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45 results on '"Attaf, Meriem"'

1. Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy

Author

Dolton, Garry, Rius, Cristina, Wall, Aaron, Szomolay, Barbara, Bianchi, Valentina, Galloway, Sarah A.E., Hasan, Md Samiul, Morin, Théo, Caillaud, Marine E., Thomas, Hannah L., Theaker, Sarah, Tan, Li Rong, Fuller, Anna, Topley, Katie, Legut, Mateusz, Attaf, Meriem, Hopkins, Jade R., Behiry, Enas, Zabkiewicz, Joanna, Alvares, Caroline, Lloyd, Angharad, Rogers, Amber, Henley, Peter, Fegan, Christopher, Ottmann, Oliver, Man, Stephen, Crowther, Michael D., Donia, Marco, Svane, Inge Marie, Cole, David K., Brown, Paul E., Rizkallah, Pierre, and Sewell, Andrew K.

Published
2023
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2. CD4+ T Cells Recognize Conserved Influenza A Epitopes through Shared Patterns of V-Gene Usage and Complementary Biochemical Features

Author

Greenshields-Watson, Alexander, Attaf, Meriem, MacLachlan, Bruce J., Whalley, Thomas, Rius, Cristina, Wall, Aaron, Lloyd, Angharad, Hughes, Hywel, Strange, Kathryn E., Mason, Georgina H., Schauenburg, Andrea J., Hulin-Curtis, Sarah L., Geary, James, Chen, Yuan, Lauder, Sarah N., Smart, Kathryn, Vijaykrishna, Dhanasekaran, Grau, Miguel L., Shugay, Mikhail, Andrews, Robert, Dolton, Garry, Rizkallah, Pierre J., Gallimore, Awen M., Sewell, Andrew K., Godkin, Andrew J., and Cole, David K.

Published
2020
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3. Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1

Author

Crowther, Michael D., Dolton, Garry, Legut, Mateusz, Caillaud, Marine E., Lloyd, Angharad, Attaf, Meriem, Galloway, Sarah A. E., Rius, Cristina, Farrell, Colin P., Szomolay, Barbara, Ager, Ann, Parker, Alan L., Fuller, Anna, Donia, Marco, McCluskey, James, Rossjohn, Jamie, Svane, Inge Marie, Phillips, John D., and Sewell, Andrew K.

Published
2020
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4. Functional analysis of T cells lacking germline-encoded complementarity-determining regions

Author

Attaf, Meriem and Dyson, Julian

Subjects
610
Abstract

The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognising virtually any pathogen. It has been known for several decades that T lymphocytes recognise short peptides derived from degraded proteins that are presented by major histocompatibility complex (MHC) molecules. Nonetheless, the molecular basis of this interaction is still a matter of debate, the central issue being the roles played by the complementarity-determining regions (CDR) in this context. In this study we have generated a transgenic mouse line lacking all three TCR-β chain CDR loops and a second line lacking the hypervariable CDR3 loop only. This project is the first attempt to characterise such transgenic mice, which were found to develop normally and to generate functional T lymphocytes. We demonstrate that in this murine TCR-β transgenic system, CDR-modified thymocytes can be selected on MHC and develop into functional peripheral T cells. We show for the first time that T cells lacking all three TCR-β chain CDR loops respond to protein antigen in an MHC-restricted manner. This will provide insight into the structural basis of the TCR-MHC-peptide interaction and increase our current knowledge of the requirements for the selection and functionality of MHC-restricted T cells.

Published
2013
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5. Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry

Author

Miles, John J., Tan, Mai Ping, Dolton, Garry, Edwards, Emily S.J., Galloway, Sarah A.E., Laugel, Bruno, Clement, Mathew, Makinde, Julia, Ladell, Kristin, Matthews, Katherine K., Watkins, Thomas S., Tungatt, Katie, Wong, Yide, Lee, Han Siean, Clark, Richard J., Pentier, Johanne M., Attaf, Meriem, Lissina, Anya, Ager, Ann, Gallimore, Awen, Rizkallah, Pierre J., Gras, Stephanie, Rossjohn, Jamie, Burrows, Scott R., Cole, David K., Price, David A., and Sewell, Andrew K.

Subjects
Combinatorial chemistry -- Health aspects -- Methods, Synthetic biology -- Research, Influenza vaccines -- Research, Biomimetics -- Health aspects -- Usage, Polypeptides -- Health aspects -- Chemical properties, Pharmacological research, Health care industry
Abstract

Polypeptide vaccines effectively activate human T cells but suffer from poor biological stability, which confines both transport logistics and in vivo therapeutic activity. Synthetic biology has the potential to address these limitations through the generation of highly stable antigenic 'mimics' using subunits that do not exist in the natural world. We developed a platform based on D-amino acid combinatorial chemistry and used this platform to reverse engineer a fully artificial [CD8.sup.+] T cell agonist that mirrored the immunogenicity profile of a native epitope blueprint from influenza virus. This nonnatural peptide was highly stable in human serum and gastric acid, reflecting an intrinsic resistance to physical and enzymatic degradation. In vitro, the synthetic agonist stimulated and expanded an archetypal repertoire of polyfunctional human influenza virus-specific [CD8.sup.+] T cells. In vivo, specific responses were elicited in naive humanized mice by subcutaneous vaccination, conferring protection from subsequent lethal influenza challenge. Moreover, the synthetic agonist was immunogenic after oral administration. This proof-of-concept study highlights the power of synthetic biology to expand the horizons of vaccine design and therapeutic delivery., Introduction [CD8.sup.+] T cells recognize short peptide fragments presented by MHC class I (MHC-I) molecules on the surface of nucleated cells (1-3). These peptide-MHC-I (pMHC-I) molecular arrays are scanned by [...]

Published
2018
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7. Author Correction: Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1

Author

Crowther, Michael D., Dolton, Garry, Legut, Mateusz, Caillaud, Marine E., Lloyd, Angharad, Attaf, Meriem, Galloway, Sarah A. E., Rius, Cristina, Farrell, Colin P., Szomolay, Barbara, Ager, Ann, Parker, Alan L., Fuller, Anna, Donia, Marco, McCluskey, James, Rossjohn, Jamie, Svane, Inge Marie, Phillips, John D., and Sewell, Andrew K.

Published
2020
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8. The T-cell receptor is not hardwired to engage MHC ligands

Author

Holland, Stephen J., Bartok, Istvan, Attaf, Meriem, Genolet, Raphael, Luescher, Immanuel F., Kotsiou, Eleni, Richard, Ashkenaz, Wang, Edward, White, Matthew, Coe, David J., Chai, Jian-Guo, Ferreira, Cristina, and Dyson, Julian

Published
2012

9. VDJdb in 2019: database extension, new analysis infrastructure and a T-cell receptor motif compendium

Author

Bagaev, Dmitry V, Vroomans, Renske M A, Samir, Jerome, Stervbo, Ulrik, Rius, Cristina, Dolton, Garry, Greenshields-Watson, Alexander, Attaf, Meriem, Egorov, Evgeny S, Zvyagin, Ivan V, Babel, Nina, Cole, David K, Godkin, Andrew J, Sewell, Andrew K, Kesmir, Can, Chudakov, Dmitriy M, Luciani, Fabio, Shugay, Mikhail, Bagaev, Dmitry V, Vroomans, Renske M A, Samir, Jerome, Stervbo, Ulrik, Rius, Cristina, Dolton, Garry, Greenshields-Watson, Alexander, Attaf, Meriem, Egorov, Evgeny S, Zvyagin, Ivan V, Babel, Nina, Cole, David K, Godkin, Andrew J, Sewell, Andrew K, Kesmir, Can, Chudakov, Dmitriy M, Luciani, Fabio, and Shugay, Mikhail

Abstract

Here, we report an update of the VDJdb database with a substantial increase in the number of T-cell receptor (TCR) sequences and their cognate antigens. The update further provides a new database infrastructure featuring two additional analysis modes that facilitate database querying and real-world data analysis. The increased yield of TCR specificity identification methods and the overall increase in the number of studies in the field has allowed us to expand the database more than 5-fold. Furthermore, several new analysis methods are included. For example, batch annotation of TCR repertoire sequencing samples allows for annotating large datasets on-line. Using recently developed bioinformatic methods for TCR motif mining, we have built a reduced set of high-quality TCR motifs that can be used for both training TCR specificity predictors and matching against TCRs of interest. These additions enhance the versatility of the VDJdb in the task of exploring T-cell antigen specificities. The database is available at https://vdjdb.cdr3.net.

Published
2020

10. VDJdb in 2019: database extension, new analysis infrastructure and a T-cell receptor motif compendium

Author

Sub Theoretical Biology, Theoretical Biology and Bioinformatics, Bagaev, Dmitry V, Vroomans, Renske M A, Samir, Jerome, Stervbo, Ulrik, Rius, Cristina, Dolton, Garry, Greenshields-Watson, Alexander, Attaf, Meriem, Egorov, Evgeny S, Zvyagin, Ivan V, Babel, Nina, Cole, David K, Godkin, Andrew J, Sewell, Andrew K, Kesmir, Can, Chudakov, Dmitriy M, Luciani, Fabio, Shugay, Mikhail, Sub Theoretical Biology, Theoretical Biology and Bioinformatics, Bagaev, Dmitry V, Vroomans, Renske M A, Samir, Jerome, Stervbo, Ulrik, Rius, Cristina, Dolton, Garry, Greenshields-Watson, Alexander, Attaf, Meriem, Egorov, Evgeny S, Zvyagin, Ivan V, Babel, Nina, Cole, David K, Godkin, Andrew J, Sewell, Andrew K, Kesmir, Can, Chudakov, Dmitriy M, Luciani, Fabio, and Shugay, Mikhail

Published
2020

14. GPU-Accelerated Discovery of Pathogen-Derived Molecular Mimics of a T-Cell Insulin Epitope

Author

Whalley, Thomas, primary, Dolton, Garry, additional, Brown, Paul E., additional, Wall, Aaron, additional, Wooldridge, Linda, additional, van den Berg, Hugo, additional, Fuller, Anna, additional, Hopkins, Jade R., additional, Crowther, Michael D., additional, Attaf, Meriem, additional, Knight, Robin R., additional, Cole, David K., additional, Peakman, Mark, additional, Sewell, Andrew K., additional, and Szomolay, Barbara, additional

Published
2020
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15. Peptide Super-Agonist Enhances T-Cell Responses to Melanoma

Author

Galloway, Sarah A E, Dolton, Garry, Attaf, Meriem, Wall, Aaron, Fuller, Anna, Rius, Cristina, Bianchi, Valentina, Theaker, Sarah, Lloyd, Angharad, Caillaud, Marine E, Svane, Inge Marie, Donia, Marco, Cole, David K, Szomolay, Barbara, Rizkallah, Pierre, Sewell, Andrew K, Galloway, Sarah A E, Dolton, Garry, Attaf, Meriem, Wall, Aaron, Fuller, Anna, Rius, Cristina, Bianchi, Valentina, Theaker, Sarah, Lloyd, Angharad, Caillaud, Marine E, Svane, Inge Marie, Donia, Marco, Cole, David K, Szomolay, Barbara, Rizkallah, Pierre, and Sewell, Andrew K

Abstract

Recent immunotherapeutic approaches using adoptive cell therapy, or checkpoint blockade, have demonstrated the powerful anti-cancer potential of CD8 cytotoxic T-lymphocytes (CTL). While these approaches have shown great promise, they are only effective in some patients with some cancers. The potential power, and relative ease, of therapeutic vaccination against tumour associated antigens (TAA) present in different cancers has been a long sought-after approach for harnessing the discriminating sensitivity of CTL to treat cancer and has seen recent renewed interest following cancer vaccination successes using unique tumour neoantigens. Unfortunately, results with TAA-targeted "universal" cancer vaccines (UCV) have been largely disappointing. Infectious disease models have demonstrated that T-cell clonotypes that recognise the same antigen should not be viewed as being equally effective. Extrapolation of this notion to UCV would suggest that the quality of response in terms of the T-cell receptor (TCR) clonotypes induced might be more important than the quantity of the response. Unfortunately, there is little opportunity to assess the effectiveness of individual T-cell clonotypes in vivo. Here, we identified effective, persistent T-cell clonotypes in an HLA A2+ patient following successful tumour infiltrating lymphocyte (TIL) therapy. One such T-cell clone was used to generate super-agonist altered peptide ligands (APLs). Further refinement produced an APL that was capable of inducing T-cells in greater magnitude, and with improved effectiveness, from the blood of all 14 healthy donors tested. Importantly, this APL also induced T-cells from melanoma patient blood that exhibited superior recognition of the patient's own tumour compared to those induced by the natural antigen sequence. These results suggest that use of APL to skew the clonotypic quality of T-cells induced by cancer vaccination could provide a promising avenue in the hunt for the UCV "magic bullet."

Published
2019

16. Major TCR repertoire perturbation by immunodominant HLA-B*44:03 - restricted CMV - specific T cells

Author

Attaf, Meriem, Malik, Amna, Severinsen, Mai C., Roider, Julia, Ogongo, Paul, Buus, Søren, Ndung'u, Thumbi, Leslie, Alasdair, Kløverpris, Henrik N., Matthews, Philippa C., Sewell, Andrew K., and Goulder, Philip

Abstract

Lack of disease during chronic human cytomegalovirus (CMV) infection depends on the maintenance of a high-frequency CMV-specific T cell response. The composition of the T cell receptor (TCR) repertoire underlying this response remains poorly characterised, especially within African populations in which CMV is endemic from infancy. Here we focus on the immunodominant CD8+ T cell response to the immediate-early 2 (IE-2)-derived epitope NEGVKAAW (NW8) restricted by HLA-B*44:03, a highly prevalent response in African populations, which in some subjects represents >10% of the circulating CD8+ T cells. Using pMHC multimer staining and sorting of NW8-specific T cells, the TCR repertoire raised against NW8 was characterised here using high-throughput sequencing in 20 HLA-B*44:03 subjects. We found that the CD8+ T cell repertoire raised in response to NW8 was highly skewed and featured preferential use of a restricted set of V and J gene segments. Furthermore, as often seen in immunity against ancient viruses like CMV and Epstein-Barr virus (EBV), the response was strongly dominated by identical TCR sequences shared by multiple individuals, or “public” TCRs. Finally, we describe a pair “superdominant” TCR clonotypes, which were germline or nearly germline-encoded and produced at remarkably high frequencies in certain individuals, with a single CMV-specific clonotype representing up to 17% of all CD8+ T cells. Given the magnitude of the NW8 response, we propose that this major skewing of CMV-specific immunity leads to massive perturbations in the overall TCR repertoire in HLA-B*44:03 individuals

Published
2018

18. Peptide-MHC class 1 tetramers can fail to detect relevant functional T cell clonotypes and underestimate antigen-reactive T cell populations

Author

Rius, Cristina, Attaf, Meriem, Tungatt, Katie, Bianchi, Valentina, Legut, Mateusz, Bovay, Amandine, Donia, Marco, Straten, Per thor, Peakman, Mark, Svane, Inge Marie, Ott, Sascha, Connor, Tom, Szomolay, Barbara, Dolton, Garry, and Sewell, Andrew K.

Subjects
chemical and pharmacologic phenomena
Abstract

Peptide-MHC (pMHC) multimers, usually used as streptavidin-based tetramers, have transformed the study of Ag-specific T cells by allowing direct detection, phenotyping, and enumeration within polyclonal T cell populations. These reagents are now a standard part of the immunology toolkit and have been used in many thousands of published studies. Unfortunately, the TCR-affinity threshold required for staining with standard pMHC multimer protocols is higher than that required for efficient T cell activation. This discrepancy makes it possible for pMHC multimer staining to miss fully functional T cells, especially where low-affinity TCRs predominate, such as in MHC class II-restricted responses or those directed against self-antigens. Several recent, somewhat alarming, reports indicate that pMHC staining might fail to detect the majority of functional T cells and have prompted suggestions that T cell immunology has become biased toward the type of cells amenable to detection with multimeric pMHC. We use several viral- and tumor-specific pMHC reagents to compare populations of human T cells stained by standard pMHC protocols and optimized protocols that we have developed. Our results confirm that optimized protocols recover greater populations of T cells that include fully functional T cell clonotypes that cannot be stained by regular pMHC-staining protocols. These results highlight the importance of using optimized procedures that include the use of protein kinase inhibitor and Ab cross-linking during staining to maximize the recovery of Ag-specific T cells and serve to further highlight that many previous quantifications of T cell responses with pMHC reagents are likely to have considerably underestimated the size of the relevant populations.

Published
2018

19. Peptide-MHC Class I Tetramers Can Fail To Detect Relevant Functional T Cell Clonotypes and Underestimate Antigen-Reactive T Cell Populations

Author

Rius, Cristina, Attaf, Meriem, Tungatt, Katie, Bianchi, Valentina, Legut, Mateusz, Bovay, Amandine, Donia, Marco, thor Straten, Per, Peakman, Mark, Svane, Inge Marie, Ott, Sascha, Connor, Tom, Szomolay, Barbara, Dolton, Garry, and Sewell, Andrew K.

Subjects
Herpesvirus 4, Human/immunology, Herpesvirus 4, Human, Cytomegalovirus/immunology, Melanoma/immunology, RNA-Binding Proteins/immunology, Receptors, Antigen, T-Cell, Cytomegalovirus, chemical and pharmacologic phenomena, CD8-Positive T-Lymphocytes, Lymphocyte Activation/immunology, Lymphocyte Activation, CD8-Positive T-Lymphocytes/immunology, Lymphocytes, Tumor-Infiltrating, Antigen Recognition and Responses, HLA-A2 Antigen, Tumor Cells, Cultured, Humans, Melanoma, Protein Kinase Inhibitors, Lymphocytes, Tumor-Infiltrating/immunology, HLA-A2 Antigen/immunology, Orthomyxoviridae/immunology, Protein Binding/immunology, Protein Kinase Inhibitors/metabolism, Receptors, Antigen, T-Cell/immunology, Staining and Labeling/methods, Staining and Labeling, RNA-Binding Proteins, Orthomyxoviridae, Protein Binding
Abstract

Peptide-MHC (pMHC) multimers, usually used as streptavidin-based tetramers, have transformed the study of Ag-specific T cells by allowing direct detection, phenotyping, and enumeration within polyclonal T cell populations. These reagents are now a standard part of the immunology toolkit and have been used in many thousands of published studies. Unfortunately, the TCR-affinity threshold required for staining with standard pMHC multimer protocols is higher than that required for efficient T cell activation. This discrepancy makes it possible for pMHC multimer staining to miss fully functional T cells, especially where low-affinity TCRs predominate, such as in MHC class II-restricted responses or those directed against self-antigens. Several recent, somewhat alarming, reports indicate that pMHC staining might fail to detect the majority of functional T cells and have prompted suggestions that T cell immunology has become biased toward the type of cells amenable to detection with multimeric pMHC. We use several viral- and tumor-specific pMHC reagents to compare populations of human T cells stained by standard pMHC protocols and optimized protocols that we have developed. Our results confirm that optimized protocols recover greater populations of T cells that include fully functional T cell clonotypes that cannot be stained by regular pMHC-staining protocols. These results highlight the importance of using optimized procedures that include the use of protein kinase inhibitor and Ab cross-linking during staining to maximize the recovery of Ag-specific T cells and serve to further highlight that many previous quantifications of T cell responses with pMHC reagents are likely to have considerably underestimated the size of the relevant populations.

Published
2018
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20. VDJdb in 2019: database extension, new analysis infrastructure and a T-cell receptor motif compendium

Author

Bagaev, Dmitry V, primary, Vroomans, Renske M A, additional, Samir, Jerome, additional, Stervbo, Ulrik, additional, Rius, Cristina, additional, Dolton, Garry, additional, Greenshields-Watson, Alexander, additional, Attaf, Meriem, additional, Egorov, Evgeny S, additional, Zvyagin, Ivan V, additional, Babel, Nina, additional, Cole, David K, additional, Godkin, Andrew J, additional, Sewell, Andrew K, additional, Kesmir, Can, additional, Chudakov, Dmitriy M, additional, Luciani, Fabio, additional, and Shugay, Mikhail, additional

Published
2019
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21. Peptide Super-Agonist Enhances T-Cell Responses to Melanoma

Author

Galloway, Sarah A. E., primary, Dolton, Garry, additional, Attaf, Meriem, additional, Wall, Aaron, additional, Fuller, Anna, additional, Rius, Cristina, additional, Bianchi, Valentina, additional, Theaker, Sarah, additional, Lloyd, Angharad, additional, Caillaud, Marine E., additional, Svane, Inge Marie, additional, Donia, Marco, additional, Cole, David K., additional, Szomolay, Barbara, additional, Rizkallah, Pierre, additional, and Sewell, Andrew K., additional

Published
2019
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22. VDJdb: a curated database of T-cell receptor sequences with known antigen specificity

Author

Shugay, Mikhail, Bagaev, Dmitriy V, Zvyagin, Ivan V, Vroomans, Renske M, Crawford, Jeremy Chase, Dolton, Garry, Komech, Ekaterina A, Sycheva, Anastasiya L, Koneva, Anna E, Egorov, Evgeniy S, Eliseev, Alexey V, Van Dyk, Ewald, Dash, Pradyot, Attaf, Meriem, Rius, Cristina, Ladell, Kristin, McLaren, James E, Matthews, Katherine K, Clemens, E Bridie, Douek, Daniel C, Luciani, Fabio, van Baarle, Debbie, Kedzierska, Katherine, Kesmir, Can, Thomas, Paul G, Price, David A, Sewell, Andrew K, Chudakov, Dmitriy M, Shugay, Mikhail, Bagaev, Dmitriy V, Zvyagin, Ivan V, Vroomans, Renske M, Crawford, Jeremy Chase, Dolton, Garry, Komech, Ekaterina A, Sycheva, Anastasiya L, Koneva, Anna E, Egorov, Evgeniy S, Eliseev, Alexey V, Van Dyk, Ewald, Dash, Pradyot, Attaf, Meriem, Rius, Cristina, Ladell, Kristin, McLaren, James E, Matthews, Katherine K, Clemens, E Bridie, Douek, Daniel C, Luciani, Fabio, van Baarle, Debbie, Kedzierska, Katherine, Kesmir, Can, Thomas, Paul G, Price, David A, Sewell, Andrew K, and Chudakov, Dmitriy M

Abstract

The ability to decode antigen specificities encapsulated in the sequences of rearranged T-cell receptor (TCR) genes is critical for our understanding of the adaptive immune system and promises significant advances in the field of translational medicine. Recent developments in high-throughput sequencing methods (immune repertoire sequencing technology, or RepSeq) and single-cell RNA sequencing technology have allowed us to obtain huge numbers of TCR sequences from donor samples and link them to T-cell phenotypes. However, our ability to annotate these TCR sequences still lags behind, owing to the enormous diversity of the TCR repertoire and the scarcity of available data on T-cell specificities. In this paper, we present VDJdb, a database that stores and aggregates the results of published T-cell specificity assays and provides a universal platform that couples antigen specificities with TCR sequences. We demonstrate that VDJdb is a versatile instrument for the annotation of TCR repertoire data, enabling a concatenated view of antigen-specific TCR sequence motifs. VDJdb can be accessed at https://vdjdb.cdr3.net and https://github.com/antigenomics/vdjdb-db.

Published
2018

23. VDJdb: a curated database of T-cell receptor sequences with known antigen specificity

Author

Sub Theoretical Biology, Theoretical Biology and Bioinformatics, Shugay, Mikhail, Bagaev, Dmitriy V, Zvyagin, Ivan V, Vroomans, Renske M, Crawford, Jeremy Chase, Dolton, Garry, Komech, Ekaterina A, Sycheva, Anastasiya L, Koneva, Anna E, Egorov, Evgeniy S, Eliseev, Alexey V, Van Dyk, Ewald, Dash, Pradyot, Attaf, Meriem, Rius, Cristina, Ladell, Kristin, McLaren, James E, Matthews, Katherine K, Clemens, E Bridie, Douek, Daniel C, Luciani, Fabio, van Baarle, Debbie, Kedzierska, Katherine, Kesmir, Can, Thomas, Paul G, Price, David A, Sewell, Andrew K, Chudakov, Dmitriy M, Sub Theoretical Biology, Theoretical Biology and Bioinformatics, Shugay, Mikhail, Bagaev, Dmitriy V, Zvyagin, Ivan V, Vroomans, Renske M, Crawford, Jeremy Chase, Dolton, Garry, Komech, Ekaterina A, Sycheva, Anastasiya L, Koneva, Anna E, Egorov, Evgeniy S, Eliseev, Alexey V, Van Dyk, Ewald, Dash, Pradyot, Attaf, Meriem, Rius, Cristina, Ladell, Kristin, McLaren, James E, Matthews, Katherine K, Clemens, E Bridie, Douek, Daniel C, Luciani, Fabio, van Baarle, Debbie, Kedzierska, Katherine, Kesmir, Can, Thomas, Paul G, Price, David A, Sewell, Andrew K, and Chudakov, Dmitriy M

Published
2018

24. Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig

Author

Tungatt, Katie, primary, Dolton, Garry, additional, Morgan, Sophie B., additional, Attaf, Meriem, additional, Fuller, Anna, additional, Whalley, Thomas, additional, Hemmink, Johanneke D., additional, Porter, Emily, additional, Szomolay, Barbara, additional, Montoya, Maria, additional, Hammond, John A., additional, Miles, John J., additional, Cole, David K., additional, Townsend, Alain, additional, Bailey, Mick, additional, Rizkallah, Pierre J., additional, Charleston, Bryan, additional, Tchilian, Elma, additional, and Sewell, Andrew K., additional

Published
2018
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25. Peptide–MHC Class I Tetramers Can Fail To Detect Relevant Functional T Cell Clonotypes and Underestimate Antigen-Reactive T Cell Populations

Author

Rius, Cristina, primary, Attaf, Meriem, additional, Tungatt, Katie, additional, Bianchi, Valentina, additional, Legut, Mateusz, additional, Bovay, Amandine, additional, Donia, Marco, additional, thor Straten, Per, additional, Peakman, Mark, additional, Svane, Inge Marie, additional, Ott, Sascha, additional, Connor, Tom, additional, Szomolay, Barbara, additional, Dolton, Garry, additional, and Sewell, Andrew K., additional

Published
2018
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26. PD-1+ Polyfunctional T Cells Dominate the Periphery after Tumor-Infiltrating Lymphocyte Therapy for Cancer

Author

Donia, Marco, Kjeldsen, Julie Westerlin, Andersen, Rikke, Westergaard, Marie Christine Wulff, Bianchi, Valentina, Legut, Mateusz, Attaf, Meriem, Szomolay, Barbara, Ott, Sascha, Dolton, Garry, Lyngaa, Rikke, Hadrup, Sine Reker, Sewell, Andrew K, Svane, Inge Marie, Donia, Marco, Kjeldsen, Julie Westerlin, Andersen, Rikke, Westergaard, Marie Christine Wulff, Bianchi, Valentina, Legut, Mateusz, Attaf, Meriem, Szomolay, Barbara, Ott, Sascha, Dolton, Garry, Lyngaa, Rikke, Hadrup, Sine Reker, Sewell, Andrew K, and Svane, Inge Marie

Abstract

Purpose: Infusion of highly heterogeneous populations of autologous tumor-infiltrating lymphocytes (TIL) can result in tumor regression of exceptional duration. Initial tumor regression has been associated with persistence of tumor-specific TILs 1 month after infusion, but mechanisms leading to long-lived memory responses are currently unknown. Here, we studied the dynamics of bulk tumor-reactive CD8+ T-cell populations in patients with metastatic melanoma following treatment with TILs.Experimental Design: We analyzed the function and phenotype of tumor-reactive CD8+ T cells contained in serial blood samples of 16 patients treated with TILs.Results: Polyfunctional tumor-reactive CD8+ T cells accumulated over time in the peripheral lymphocyte pool. Combinatorial analysis of multiple surface markers (CD57, CD27, CD45RO, PD-1, and LAG-3) showed a unique differentiation pattern of polyfunctional tumor-reactive CD8+ T cells, with highly specific PD-1 upregulation early after infusion. The differentiation and functional status appeared largely stable for up to 1 year after infusion. Despite some degree of clonal diversification occurring in vivo within the bulk tumor-reactive CD8+ T cells, further analyses showed that CD8+ T cells specific for defined tumor antigens had similar differentiation status.Conclusions: We demonstrated that tumor-reactive CD8+ T-cell subsets that persist after TIL therapy are mostly polyfunctional, display a stable partially differentiated phenotype, and express high levels of PD-1. These partially differentiated PD-1+ polyfunctional TILs have a high capacity for persistence and may be susceptible to PD-L1/PD-L2-mediated inhibition. Clin Cancer Res; 23(19); 5779-88. ©2017 AACR.

Published
2017

27. PD-1+ Polyfunctional T Cells Dominate the Periphery after Tumor-Infiltrating Lymphocyte Therapy for Cancer

Author

Donia, Marco, primary, Kjeldsen, Julie Westerlin, additional, Andersen, Rikke, additional, Westergaard, Marie Christine Wulff, additional, Bianchi, Valentina, additional, Legut, Mateusz, additional, Attaf, Meriem, additional, Szomolay, Barbara, additional, Ott, Sascha, additional, Dolton, Garry, additional, Lyngaa, Rikke, additional, Hadrup, Sine Reker, additional, Sewell, Andrew K., additional, and Svane, Inge Marie, additional

Published
2017
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28. VDJdb: a curated database of T-cell receptor sequences with known antigen specificity

Author

Shugay, Mikhail, primary, Bagaev, Dmitriy V, additional, Zvyagin, Ivan V, additional, Vroomans, Renske M, additional, Crawford, Jeremy Chase, additional, Dolton, Garry, additional, Komech, Ekaterina A, additional, Sycheva, Anastasiya L, additional, Koneva, Anna E, additional, Egorov, Evgeniy S, additional, Eliseev, Alexey V, additional, Van Dyk, Ewald, additional, Dash, Pradyot, additional, Attaf, Meriem, additional, Rius, Cristina, additional, Ladell, Kristin, additional, McLaren, James E, additional, Matthews, Katherine K, additional, Clemens, E Bridie, additional, Douek, Daniel C, additional, Luciani, Fabio, additional, van Baarle, Debbie, additional, Kedzierska, Katherine, additional, Kesmir, Can, additional, Thomas, Paul G, additional, Price, David A, additional, Sewell, Andrew K, additional, and Chudakov, Dmitriy M, additional

Published
2017
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29. The T cell antigen receptor: the Swiss army knife of the immune

Author

Attaf, Meriem, Legut, Mateusz, Cole, David, and Sewell, Andrew K.

Subjects
QR180, chemical and pharmacologic phenomena
Abstract

The mammalian T cell receptor (TCR) orchestrates immunity by responding\ud to many billions of different ligands that it has never encountered before\ud and cannot adapt to at the protein sequence level. This remarkable receptor\ud exists in two main heterodimeric isoforms: ab TCR and gd TCR. The ab\ud TCR is expressed on the majority of peripheral T cells. Most ab T cells\ud recognize peptides, derived from degraded proteins, presented at the cell\ud surface in molecular cradles called major histocompatibility complex (MHC)\ud molecules. Recent reports have described other ab T cell subsets. These\ud ‘unconventional’ T cells bear TCRs that are capable of recognizing lipid\ud ligands presented in the context of the MHC-like CD1 protein family or\ud bacterial metabolites bound to the MHC-related protein 1 (MR1). gd T cells\ud constitute a minority of the T cell pool in human blood, but can represent\ud up to half of total T cells in tissues such as the gut and skin. The identity\ud of the preferred ligands for gd T cells remains obscure, but it is now\ud known that this receptor can also functionally engage CD1-lipid, or\ud immunoglobulin (Ig) superfamily proteins called butyrophilins in the\ud presence of pyrophosphate intermediates of bacterial lipid biosynthesis.\ud Interactions between TCRs and these ligands allow the host to discriminate\ud between self and non-self and co-ordinate an attack on the latter. Here, we\ud describe how cells of the T lymphocyte lineage and their antigen receptors\ud are generated and discuss the various modes of antigen recognition by these\ud extraordinarily versatile receptors.

Published
2015

30. αβ T cell receptors as predictors of health and disease

Author

Attaf, Meriem, Huseby, Eric, and Sewell, Andrew K.

Subjects
QR180, chemical and pharmacologic phenomena, R1
Abstract

The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex (MHC) molecules at the cell surface. Interaction between peptide-MHC (pMHC) and the T cell receptor (TCR) is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR ‘signatures’ raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome.

Published
2015

34. Major TCR Repertoire Perturbation by Immunodominant HLA-B*44:03-Restricted CMV-Specific T Cells.

Author

Attaf, Meriem, Malik, Amna, Severinsen, Mai C., Roider, Julia, Ogongo, Paul, Buus, Søren, Ndung'u, Thumbi, Leslie, Alasdair, Kløverpris, Henrik N., Matthews, Philippa C., Sewell, Andrew K., and Goulder, Philip

Abstract

Lack of disease during chronic human cytomegalovirus (CMV) infection depends on the maintenance of a high-frequency CMV-specific T cell response. The composition of the T cell receptor (TCR) repertoire underlying this response remains poorly characterised, especially within African populations in which CMV is endemic from infancy. Here we focus on the immunodominant CD8+ T cell response to the immediate-early 2 (IE-2)-derived epitope NEGVKAAW (NW8) restricted by HLA-B*44:03, a highly prevalent response in African populations, which in some subjects represents >10% of the circulating CD8+ T cells. Using pMHC multimer staining and sorting of NW8-specific T cells, the TCR repertoire raised against NW8 was characterised here using high-throughput sequencing in 20 HLA-B*44:03 subjects. We found that the CD8+ T cell repertoire raised in response to NW8 was highly skewed and featured preferential use of a restricted set of V and J gene segments. Furthermore, as often seen in immunity against ancient viruses like CMV and Epstein-Barr virus (EBV), the response was strongly dominated by identical TCR sequences shared by multiple individuals, or "public" TCRs. Finally, we describe a pair "superdominant" TCR clonotypes, which were germline or nearly germline-encoded and produced at remarkably high frequencies in certain individuals, with a single CMV-specific clonotype representing up to 17% of all CD8+ T cells. Given the magnitude of the NW8 response, we propose that this major skewing of CMV-specific immunity leads to massive perturbations in the overall TCR repertoire in HLA-B*44:03 individuals. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
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36. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one: National Harbor, MD, USA. 9-13 November 2016

Author

Lundqvist, Andreas, van Hoef, Vincent, Zhang, Xiaonan, Wennerberg, Erik, Lorent, Julie, Witt, Kristina, Sanz, Laia Masvidal, Liang, Shuo, Murray, Shannon, Larsson, Ola, Kiessling, Rolf, Mao, Yumeng, Sidhom, John-William, Bessell, Catherine A., Havel, Jonathan, Schneck, Jonathan, Chan, Timothy A., Sachsenmeier, Eliot, Woods, David, Berglund, Anders, Ramakrishnan, Rupal, Sodre, Andressa, Weber, Jeffrey, Zappasodi, Roberta, Li, Yanyun, Qi, Jingjing, Wong, Philip, Sirard, Cynthia, Postow, Michael, Newman, Walter, Koon, Henry, Velcheti, Vamsidhar, Callahan, Margaret K., Wolchok, Jedd D., Merghoub, Taha, Lum, Lawrence G., Choi, Minsig, Thakur, Archana, Deol, Abhinav, Dyson, Gregory, Shields, Anthony, Haymaker, Cara, Uemura, Marc, Murthy, Ravi, James, Marihella, Wang, Daqing, Brevard, Julie, Monaghan, Catherine, Swann, Suzanne, Geib, James, Cornfeld, Mark, Chunduru, Srinivas, Agrawal, Sudhir, Yee, Cassian, Wargo, Jennifer, Patel, Sapna P., Amaria, Rodabe, Tawbi, Hussein, Glitza, Isabella, Woodman, Scott, Hwu, Wen-Jen, Davies, Michael A., Hwu, Patrick, Overwijk, Willem W., Bernatchez, Chantale, Diab, Adi, Massarelli, Erminia, Segal, Neil H., Ribrag, Vincent, Melero, Ignacio, Gangadhar, Tara C., Urba, Walter, Schadendorf, Dirk, Ferris, Robert L., Houot, Roch, Morschhauser, Franck, Logan, Theodore, Luke, Jason J., Sharfman, William, Barlesi, Fabrice, Ott, Patrick A., Mansi, Laura, Kummar, Shivaani, Salles, Gilles, Carpio, Cecilia, Meier, Roland, Krishnan, Suba, McDonald, Dan, Maurer, Matthew, Gu, Xuemin, Neely, Jaclyn, Suryawanshi, Satyendra, Levy, Ronald, Khushalani, Nikhil, Wu, Jennifer, Zhang, Jinyu, Basher, Fahmin, Rubinstein, Mark, Bucsek, Mark, Qiao, Guanxi, MacDonald, Cameron, Hylander, Bonnie, Repasky, Elizabeth, Chatterjee, Shilpak, Daenthanasanmak, Anusara, Chakraborty, Paramita, Toth, Kyle, Meek, Megan, Garrett-Mayer, Elizabeth, Nishimura, Michael, Paulos, Chrystal, Beeson, Craig, Yu, Xuezhong, Mehrotra, Shikhar, Zhao, Fei, Evans, Kathy, Xiao, Christine, Holtzhausen, Alisha, Hanks, Brent A., Scharping, Nicole, Menk, Ashley V., Moreci, Rebecca, Whetstone, Ryan, Dadey, Rebekah, Watkins, Simon, Ferris, Robert, Delgoffe, Greg M., Peled, Jonathan, Devlin, Sean, Staffas, Anna, Lumish, Melissa, Rodriguez, Kori Porosnicu, Ahr, Katya, Perales, Miguel, Giralt, Sergio, Taur, Ying, Pamer, Eric, van den Brink, Marcel R. M., Jenq, Robert, Annels, Nicola, Pandha, Hardev, Simpson, Guy, Mostafid, Hugh, Harrington, Kevin, Melcher, Alan, Grose, Mark, Davies, Bronwyn, Au, Gough, Karpathy, Roberta, Shafren, Darren, Ricca, Jacob, Zamarin, Dmitriy, Batista, Luciana, Marliot, Florence, Vasaturo, Angela, Carpentier, Sabrina, Poggionovo, Cécile, Frayssinet, Véronique, Fieschi, Jacques, Van den Eynde, Marc, Pagès, Franck, Galon, Jérôme, Hermitte, Fabienne, Smith, Sean G., Nguyen, Khue, Ravindranathan, Sruthi, Koppolu, Bhanu, Zaharoff, David, Schvartsman, Gustavo, Bassett, Roland, McQuade, Jennifer L., Haydu, Lauren E., Kline, Douglas, Chen, Xiufen, Fosco, Dominick, Kline, Justin, Overacre, Abigail, Chikina, Maria, Brunazzi, Erin, Shayan, Gulidanna, Horne, William, Kolls, Jay, Bruno, Tullia C., Workman, Creg, Vignali, Dario, Adusumilli, Prasad S., Ansa-Addo, Ephraim A, Li, Zihai, Gerry, Andrew, Sanderson, Joseph P., Howe, Karen, Docta, Roslin, Gao, Qian, Bagg, Eleanor A. L., Tribble, Nicholas, Maroto, Miguel, Betts, Gareth, Bath, Natalie, Melchiori, Luca, Lowther, Daniel E., Ramachandran, Indu, Kari, Gabor, Basu, Samik, Binder-Scholl, Gwendolyn, Chagin, Karen, Pandite, Lini, Holdich, Tom, Amado, Rafael, Zhang, Hua, Glod, John, Bernstein, Donna, Jakobsen, Bent, Mackall, Crystal, Wong, Ryan, Silk, Jonathan D., Adams, Katherine, Hamilton, Garth, Bennett, Alan D., Brett, Sara, Jing, Junping, Quattrini, Adriano, Saini, Manoj, Wiedermann, Guy, Brewer, Joanna, Duong, MyLinh, Lu, An, Chang, Peter, Mahendravada, Aruna, Shinners, Nicholas, Slawin, Kevin, Spencer, David M., Foster, Aaron E., Bayle, J. Henri, Bergamaschi, Cristina, Ng, Sinnie Sin Man, Nagy, Bethany, Jensen, Shawn, Hu, Xintao, Alicea, Candido, Fox, Bernard, Felber, Barbara, Pavlakis, George, Chacon, Jessica, Yamamoto, Tori, Garrabrant, Thomas, Cortina, Luis, Powell, Daniel J., Donia, Marco, Kjeldsen, Julie Westerlin, Andersen, Rikke, Westergaard, Marie Christine Wulff, Bianchi, Valentina, Legut, Mateusz, Attaf, Meriem, Dolton, Garry, Szomolay, Barbara, Ott, Sascha, Lyngaa, Rikke, Hadrup, Sine Reker, Sewell, Andrew Kelvin, Svane, Inge Marie, Fan, Aaron, Kumai, Takumi, Celis, Esteban, Frank, Ian, Stramer, Amanda, Blaskovich, Michelle A., Wardell, Seth, Fardis, Maria, Bender, James, Lotze, Michael T., Goff, Stephanie L., Zacharakis, Nikolaos, Assadipour, Yasmine, Prickett, Todd D., Gartner, Jared J., Somerville, Robert, Black, Mary, Xu, Hui, Chinnasamy, Harshini, Kriley, Isaac, Lu, Lily, Wunderlich, John, Robbins, Paul F., Rosenberg, Steven, Feldman, Steven A., Trebska-McGowan, Kasia, Malekzadeh, Parisa, Payabyab, Eden, Sherry, Richard, Gokuldass, Aishwarya, Kopits, Charlene, Rabinovich, Brian, Green, Daniel S., Kamenyeva, Olena, Zoon, Kathryn C., Annunziata, Christina M., Hammill, Joanne, Helsen, Christopher, Aarts, Craig, Bramson, Jonathan, Harada, Yui, Yonemitsu, Yoshikazu, Mwawasi, Kenneth, Denisova, Galina, Giri, Rajanish, Jin, Benjamin, Campbell, Tracy, Draper, Lindsey M., Stevanovic, Sanja, Yu, Zhiya, Weissbrich, Bianca, Restifo, Nicholas P., Trimble, Cornelia L., Hinrichs, Christian S., Tsang, Kwong, Fantini, Massimo, Hodge, James W., Fujii, Rika, Fernando, Ingrid, Jochems, Caroline, Heery, Christopher, Gulley, James, Soon-Shiong, Patrick, Schlom, Jeffrey, Jing, Weiqing, Gershan, Jill, Blitzer, Grace, Weber, James, McOlash, Laura, Johnson, Bryon D., Kiany, Simin, Gangxiong, Huang, Kleinerman, Eugenie S., Klichinsky, Michael, Ruella, Marco, Shestova, Olga, Kenderian, Saad, Kim, Miriam, Scholler, John, June, Carl H., Gill, Saar, Moogk, Duane, Zhong, Shi, Liadi, Ivan, Rittase, William, Fang, Victoria, Dougherty, Janna, Perez-Garcia, Arianne, Osman, Iman, Zhu, Cheng, Varadarajan, Navin, Frey, Alan, Krogsgaard, Michelle, Landi, Daniel, Fousek, Kristen, Mukherjee, Malini, Shree, Ankita, Joseph, Sujith, Bielamowicz, Kevin, Byrd, Tiara, Ahmed, Nabil, Hegde, Meenakshi, Lee, Sylvia, Byrd, David, Thompson, John, Bhatia, Shailender, Tykodi, Scott, Delismon, Judy, Chu, Liz, Abdul-Alim, Siddiq, Ohanian, Arpy, DeVito, Anna Marie, Riddell, Stanley, Margolin, Kim, Magalhaes, Isabelle, Mattsson, Jonas, Uhlin, Michael, Nemoto, Satoshi, Villarroel, Patricio Pérez, Nakagawa, Ryosuke, Mule, James J., Mailloux, Adam W., Mata, Melinda, Nguyen, Phuong, Gerken, Claudia, DeRenzo, Christopher, Gottschalk, Stephen, Mathieu, Mélissa, Pelletier, Sandy, Stagg, John, Turcotte, Simon, Minutolo, Nicholas, Sharma, Prannda, Tsourkas, Andrew, Mockel-Tenbrinck, Nadine, Mauer, Daniela, Drechsel, Katharina, Barth, Carola, Freese, Katharina, Kolrep, Ulrike, Schult, Silke, Assenmacher, Mario, Kaiser, Andrew, Mullinax, John, Hall, MacLean, Le, Julie, Kodumudi, Krithika, Royster, Erica, Richards, Allison, Gonzalez, Ricardo, Sarnaik, Amod, Pilon-Thomas, Shari, Nielsen, Morten, Krarup-Hansen, Anders, Hovgaard, Dorrit, Petersen, Michael Mørk, Loya, Anand Chainsukh, Junker, Niels, Rivas, Charlotte, Parihar, Robin, Rooney, Cliona M., Qin, Haiying, Nguyen, Sang, Su, Paul, Burk, Chad, Duncan, Brynn, Kim, Bong-Hyun, Kohler, M. Eric, Fry, Terry, Rao, Arjun A., Teyssier, Noam, Pfeil, Jacob, Sgourakis, Nikolaos, Salama, Sofie, Haussler, David, Richman, Sarah A., Nunez-Cruz, Selene, Gershenson, Zack, Mourelatos, Zissimos, Barrett, David, Grupp, Stephan, Milone, Michael, Rodriguez-Garcia, Alba, Robinson, Matthew K., Adams, Gregory P., Santos, João, Havunen, Riikka, Siurala, Mikko, Cervera-Carrascón, Víctor, Parviainen, Suvi, Antilla, Marjukka, Hemminki, Akseli, Sethuraman, Jyothi, Santiago, Laurelis, Chen, Jie Qing, Dai, Zhimin, Sha, Huizi, Su, Shu, Ding, Naiqing, Liu, Baorui, Pasetto, Anna, Helman, Sarah R., Rosenberg, Steven A., Burgess, Melissa, Zhang, Hui, Lee, Tien, Klingemann, Hans, Nghiem, Paul, Kirkwood, John M., Rossi, John M., Sherman, Marika, Xue, Allen, Shen, Yueh-wei, Navale, Lynn, Kochenderfer, James N., Bot, Adrian, Veerapathran, Anandaraman, Wiener, Doris, Waller, Edmund K., Li, Jian-Ming, Petersen, Christopher, Blazar, Bruce R., Li, Jingxia, Giver, Cynthia R., Wang, Ziming, Grossenbacher, Steven K., Sturgill, Ian, Canter, Robert J., Murphy, William J., Zhang, Congcong, Burger, Michael C., Jennewein, Lukas, Waldmann, Anja, Mittelbronn, Michel, Tonn, Torsten, Steinbach, Joachim P., Wels, Winfried S., Williams, Jason B., Zha, Yuanyuan, Gajewski, Thomas F., Williams, LaTerrica C., Krenciute, Giedre, Kalra, Mamta, Louis, Chrystal, Xin, Gang, Schauder, David, Jiang, Aimin, Joshi, Nikhil, Cui, Weiguo, Zeng, Xue, Zhao, Zeguo, Hamieh, Mohamad, Eyquem, Justin, Gunset, Gertrude, Bander, Neil, Sadelain, Michel, Askmyr, David, Abolhalaj, Milad, Lundberg, Kristina, Greiff, Lennart, Lindstedt, Malin, Angell, Helen K., Kim, Kyoung-Mee, Kim, Seung-Tae, Kim, Sung, Sharpe, Alan D., Ogden, Julia, Davenport, Anna, Hodgson, Darren R., Barrett, Carl, Lee, Jeeyun, Kilgour, Elaine, Hanson, Jodi, Caspell, Richard, Karulin, Alexey, Lehmann, Paul, Ansari, Tameem, Schiller, Annemarie, Sundararaman, Srividya, Roen, Diana, Ayers, Mark, Levitan, Diane, Arreaza, Gladys, Liu, Fang, Mogg, Robin, Bang, Yung-Jue, O’Neil, Bert, Cristescu, Razvan, Friedlander, Philip, Wassman, Karl, Kyi, Chrisann, Oh, William, Bhardwaj, Nina, Bornschlegl, Svetlana, Gustafson, Michael P., Gastineau, Dennis A., Parney, Ian F., Dietz, Allan B., Carvajal-Hausdorf, Daniel, Mani, Nikita, Schalper, Kurt, Rimm, David, Chang, Serena, Kurland, John, Ahlers, Christoph Matthias, Jure-Kunkel, Maria, Cohen, Lewis, Maecker, Holden, Kohrt, Holbrook, Chen, Shuming, Crabill, George, Pritchard, Theresa, McMiller, Tracee, Pardoll, Drew, Pan, Fan, Topalian, Suzanne, Danaher, Patrick, Warren, Sarah, Dennis, Lucas, White, Andrew M., D’Amico, Leonard, Geller, Melissa, Disis, Mary L., Beechem, Joseph, Odunsi, Kunle, Fling, Steven, Derakhshandeh, Roshanak, Webb, Tonya J., Dubois, Sigrid, Conlon, Kevin, Bryant, Bonita, Hsu, Jennifer, Beltran, Nancy, Müller, Jürgen, Waldmann, Thomas, Duhen, Rebekka, Duhen, Thomas, Thompson, Lucas, Montler, Ryan, Weinberg, Andrew, Kates, Max, Early, Brandon, Yusko, Erik, Schreiber, Taylor H., Bivalacqua, Trinity J., Lunceford, Jared, Nebozhyn, Michael, Murphy, Erin, Loboda, Andrey, Kaufman, David R., Albright, Andrew, Cheng, Jonathan, Kang, S. Peter, Shankaran, Veena, Piha-Paul, Sarina A., Yearley, Jennifer, Seiwert, Tanguy, Ribas, Antoni, McClanahan, Terrill K., Sher, Xinwei, Liu, Xiao Qiao, Joe, Andrew, Plimack, Elizabeth, Forrest-Hay, Alex, Guyre, Cheryl A., Narumiya, Kohei, Delcommenne, Marc, Hirsch, Heather A., Deshpande, Amit, Reeves, Jason, Shu, Jenny, Zi, Tong, Michaelson, Jennifer, Law, Debbie, Trehu, Elizabeth, Sathyanaryanan, Sriram, Hodkinson, Brendan P., Hutnick, Natalie A., Schaffer, Michael E., Gormley, Michael, Hulett, Tyler, Ballesteros-Merino, Carmen, Dubay, Christopher, Afentoulis, Michael, Reddy, Ashok, David, Larry, Jayant, Kumar, Agrawal, Swati, Agrawal, Rajendra, Jeyakumar, Ghayathri, Kim, Seongho, Kim, Heejin, Silski, Cynthia, Suisham, Stacey, Heath, Elisabeth, Vaishampayan, Ulka, Vandeven, Natalie, Viller, Natasja Nielsen, O’Connor, Alison, Chen, Hui, Bossen, Bolette, Sievers, Eric, Uger, Robert, Johnson, Lisa, Kao, Hsiang-Fong, Hsiao, Chin-Fu, Lai, Shu-Chuan, Wang, Chun-Wei, Ko, Jenq-Yuh, Lou, Pei-Jen, Lee, Tsai-Jan, Liu, Tsang-Wu, Hong, Ruey-Long, Kearney, Staci J., Black, Joshua C., Landis, Benjamin J., Koegler, Sally, Hirsch, Brooke, Gianani, Roberto, Kim, Jeffrey, He, Ming-Xiao, Zhang, Bingqing, Su, Nan, Luo, Yuling, Ma, Xiao-Jun, Park, Emily, Kim, Dae Won, Copploa, Domenico, Kothari, Nishi, doo Chang, Young, Kim, Richard, Kim, Namyong, Lye, Melvin, Wan, Ee, Knaus, Hanna A., Berglund, Sofia, Hackl, Hubert, Karp, Judith E., Gojo, Ivana, Luznik, Leo, Hong, Henoch S., Koch, Sven D., Scheel, Birgit, Gnad-Vogt, Ulrike, Kallen, Karl-Josef, Wiegand, Volker, Backert, Linus, Kohlbacher, Oliver, Hoerr, Ingmar, Fotin-Mleczek, Mariola, Billingsley, James M., Koguchi, Yoshinobu, Conrad, Valerie, Miller, William, Gonzalez, Iliana, Poplonski, Tomasz, Meeuwsen, Tanisha, Howells-Ferreira, Ana, Rattray, Rogan, Campbell, Mary, Bifulco, Carlo, Bahjat, Keith, Curti, Brendan, Vetsika, E-K, Kallergi, G., Aggouraki, Despoina, Lyristi, Z., Katsarlinos, P., Koinis, Filippos, Georgoulias, V., Kotsakis, Athanasios, Martin, Nathan T., Aeffner, Famke, Cerkovnik, Logan, Pratte, Luke, Kim, Rebecca, Krueger, Joseph, Martínez-Usatorre, Amaia, Jandus, Camilla, Donda, Alena, Carretero-Iglesia, Laura, Speiser, Daniel E., Zehn, Dietmar, Rufer, Nathalie, Romero, Pedro, Panda, Anshuman, Mehnert, Janice, Hirshfield, Kim M., Riedlinger, Greg, Damare, Sherri, Saunders, Tracie, Sokol, Levi, Stein, Mark, Poplin, Elizabeth, Rodriguez-Rodriguez, Lorna, Silk, Ann, Chan, Nancy, Frankel, Melissa, Kane, Michael, Malhotra, Jyoti, Aisner, Joseph, Kaufman, Howard L., Ali, Siraj, Ross, Jeffrey, White, Eileen, Bhanot, Gyan, Ganesan, Shridar, Monette, Anne, Bergeron, Derek, Amor, Amira Ben, Meunier, Liliane, Caron, Christine, Morou, Antigoni, Kaufmann, Daniel, Liberman, Moishe, Jurisica, Igor, Mes-Masson, Anne-Marie, Hamzaoui, Kamel, Lapointe, Rejean, Mongan, Ann, Ku, Yuan-Chieh, Tom, Warren, Sun, Yongming, Pankov, Alex, Looney, Tim, Au-Young, Janice, Hyland, Fiona, Conroy, Jeff, Morrison, Carl, Glenn, Sean, Burgher, Blake, Ji, He, Gardner, Mark, Omilian, Angela R., Bshara, Wiam, Angela, Omilian, Obeid, Joseph M., Erdag, Gulsun, Smolkin, Mark E., Deacon, Donna H., Patterson, James W., Chen, Lieping, Bullock, Timothy N., Slingluff, Craig L., Loffredo, John T., Vuyyuru, Raja, Beyer, Sophie, Spires, Vanessa M., Fox, Maxine, Ehrmann, Jon M., Taylor, Katrina A., Korman, Alan J., Graziano, Robert F., Page, David, Sanchez, Katherine, Martel, Maritza, De Macedo, Mariana Petaccia, Qin, Yong, Reuben, Alex, Spencer, Christine, Guindani, Michele, Racolta, Adriana, Kelly, Brian, Jones, Tobin, Polaske, Nathan, Theiss, Noah, Robida, Mark, Meridew, Jeffrey, Habensus, Iva, Zhang, Liping, Pestic-Dragovich, Lidija, Tang, Lei, Sullivan, Ryan J., Olencki, Thomas, Hutson, Thomas, Roder, Joanna, Blackmon, Shauna, Roder, Heinrich, Stewart, John, Amin, Asim, Ernstoff, Marc S., Clark, Joseph I., Atkins, Michael B., Sosman, Jeffrey, McDermott, David F., Kluger, Harriet, Halaban, Ruth, Snzol, Mario, Asmellash, Senait, Steingrimsson, Arni, Wang, Chichung, Roman, Kristin, Clement, Amanda, Downing, Sean, Hoyt, Clifford, Harder, Nathalie, Schmidt, Guenter, Schoenmeyer, Ralf, Brieu, Nicolas, Yigitsoy, Mehmet, Madonna, Gabriele, Botti, Gerardo, Grimaldi, Antonio, Ascierto, Paolo A., Huss, Ralf, Athelogou, Maria, Hessel, Harald, Buchner, Alexander, Stief, Christian, Binnig, Gerd, Kirchner, Thomas, Sellappan, Shankar, Thyparambil, Sheeno, Schwartz, Sarit, Cecchi, Fabiola, Nguyen, Andrew, Vaske, Charles, Hembrough, Todd, Spacek, Jan, Vocka, Michal, Zavadova, Eva, Skalova, Helena, Dundr, Pavel, Petruzelka, Lubos, Francis, Nicole, Tilman, Rau T., Hartmann, Arndt, Netikova, Irena, Stump, Julia, Tufman, Amanda, Berger, Frank, Neuberger, Michael, Hatz, Rudolf, Lindner, Michael, Sanborn, Rachel E., Handy, John, Huber, Rudolf M., Winter, Hauke, Reu, Simone, Sun, Cheng, Xiao, Weihua, Tian, Zhigang, Arora, Kshitij, Desai, Niyati, Kulkarni, Anupriya, Rajurkar, Mihir, Rivera, Miguel, Deshpande, Vikram, Ting, David, Tsai, Katy, Nosrati, Adi, Goldinger, Simone, Hamid, Omid, Algazi, Alain, Tumeh, Paul, Hwang, Jimmy, Liu, Jacqueline, Chen, Lawrence, Dummer, Reinhard, Rosenblum, Michael, Daud, Adil, Tsao, Tsu-Shuen, Ashworth-Sharpe, Julia, Johnson, Donald, Bhaumik, Srabani, Bieniarz, Christopher, Couto, Joseph, Farrell, Michael, Ghaffari, Mahsa, Hubbard, Antony, Kosmeder, Jerome, Lee, Cleo, Marner, Erin, Uribe, Diana, Zhang, Hongjun, Zhang, Jian, Zhang, Wenjun, Zhu, Yifei, Morrison, Larry, Tsujikawa, Takahiro, Borkar, Rohan N., Azimi, Vahid, Kumar, Sushil, Thibault, Guillaume, Mori, Motomi, El Rassi, Edward, Clayburgh, Daniel R., Kulesz-Martin, Molly F., Flint, Paul W., Coussens, Lisa M., Villabona, Lisa, Masucci, Giuseppe V., Geiss, Gary, Birditt, Brian, Mei, Qian, Huang, Alan, Eagan, Maribeth A., Ignacio, Eduardo, Elliott, Nathan, Dunaway, Dwayne, Jung, Jaemyeong, Merritt, Chris, Sprague, Isaac, Webster, Philippa, Liang, Yan, Wenthe, Jessica, Enblad, Gunilla, Karlsson, Hannah, Essand, Magnus, Savoldo, Barbara, Dotti, Gianpietro, Höglund, Martin, Brenner, Malcolm K., Hagberg, Hans, Loskog, Angelica, Bernett, Matthew J., Moore, Gregory L., Hedvat, Michael, Bonzon, Christine, Chu, Seung, Rashid, Rumana, Avery, Kendra N., Muchhal, Umesh, Desjarlais, John, Kraman, Matthew, Kmiecik, Katarzyna, Allen, Natalie, Faroudi, Mustapha, Zimarino, Carlo, Wydro, Mateusz, Doody, Jacqueline, Srinivasa, Sreesha P., Govindappa, Nagaraja, Reddy, Praveen, Dubey, Aparajita, Periyasamy, Sankar, Adekandi, Madhukara, Dey, Chaitali, Joy, Mary, van Loo, Pieter Fokko, Veninga, Henrike, Shamsili, Setareh, Throsby, Mark, Dolstra, Harry, Bakker, Lex, Alva, Ajjai, Gschwendt, Juergen, Loriot, Yohann, Bellmunt, Joaquim, Feng, Dai, Poehlein, Christian, Powles, Thomas, Antonarakis, Emmanuel S., Drake, Charles G., Wu, Haiyan, De Bono, Johann, Bannerji, Rajat, Byrd, John, Gregory, Gareth, Opat, Stephen, Shortt, Jake, Yee, Andrew J., Raje, Noopur, Thompson, Seth, Balakumaran, Arun, Kumar, Shaji, Rini, Brian I., Choueiri, Toni K., Mariani, Mariangela, Albiges, Laurence, Haanen, John B., Larkin, James, Schmidinger, Manuela, Magazzù, Domenico, di Pietro, Alessandra, Motzer, Robert J., Borch, Troels Holz, Kongsted, Per, Pedersen, Magnus, Met, Özcan, Boudadi, Karim, Wang, Hao, Vasselli, James, Baughman, Jan E., Wigginton, Jon, Abdallah, Rehab, Ross, Ashley, Park, Jiwon, Grossenbacher, Steven, Luna, Jesus I., Withers, Sita, Culp, William, Chen, Mingyi, Monjazeb, Arta, Kent, Michael S., Chandran, Smita, Danforth, David, Yang, James, Klebanoff, Christopher, Goff, Stephanie, Paria, Biman, Sabesan, Arvind, Srivastava, Abhishek, Kammula, Udai, Richards, Jon, Faries, Mark, Andtbacka, Robert H. I., Diaz, Luis A., Le, Dung T., Yoshino, Takayuki, André, Thierry, Bendell, Johanna, Koshiji, Minori, Zhang, Yayan, Kang, S Peter, Lam, Bao, Jäger, Dirk, Bauer, Todd M., Wang, Judy S., Lee, Jean K., Manji, Gulam A., Kudchadkar, Ragini, Kauh, John S., Tang, Shande, Laing, Naomi, Falchook, Gerald, Garon, Edward B., Halmos, Balazs, Rina, Hui, Leighl, Natasha, Lee, Sung Sook, Walsh, William, Dragnev, Konstanin, Piperdi, Bilal, Rodriguez, Luis Paz-Ares, Shinwari, Nabeegha, Wei, Ziewn, Maas, Mary L, Deeds, Michael, Armstrong, Adam, Peterson, Tim, Steinmetz, Sue, Herzog, Thomas, Backes, Floor J., Copeland, Larry, Del Pilar Estevez Diz, Maria, Hare, Thomas W., Huh, Warner, Kim, Byoung-Gie, Moore, Kathleen M., Oaknin, Ana, Small, William, Tewari, Krishnansu S., Monk, Bradley J., Kamat, Ashish M., Nam, Kijoeng, De Santis, Maria, Dreicer, Robert, Hahn, Noah M., Perini, Rodolfo, Siefker-Radtke, Arlene, Sonpavde, Guru, de Wit, Ronald, Witjes, J. Alfred, Keefe, Stephen, Bajorin, Dean, Armand, Philippe, Kuruvilla, John, Moskowitz, Craig, Hamadani, Mehdi, Zinzani, Pier Luigi, Chlosta, Sabine, Bartlett, Nancy, Sabado, Rachel, Saenger, Yvonne, William, Loging, Donovan, Michael Joseph, Sacris, Erlinda, Mandeli, John, Salazar, Andres M., Powderly, John, Brody, Joshua, Nemunaitis, John, Emens, Leisha, Patnaik, Amita, McCaffery, Ian, Miller, Richard, Laport, Ginna, Coveler, Andrew L., Smith, David C., Grilley-Olson, Juneko E., Goel, Sanjay, Gardai, Shyra J., Law, Che-Leung, Means, Gary, Manley, Thomas, Marrone, Kristen A., Rosner, Gary, Anagnostou, Valsamo, Riemer, Joanne, Wakefield, Jessica, Zanhow, Cynthia, Baylin, Stephen, Gitlitz, Barbara, Brahmer, Julie, Signoretti, Sabina, Li, Wenting, Schloss, Charles, Michot, Jean-Marie, Ding, Wei, Christian, Beth, Marinello, Patricia, Shipp, Margaret, Najjar, Yana G., Lin, Butterfield, Lisa H., Tarhini, Ahmad A., Davar, Diwakar, Zarour, Hassane, Rush, Elizabeth, Sander, Cindy, Fu, Siqing, Bauer, Todd, Molineaux, Chris, Bennett, Mark K., Orford, Keith W., Papadopoulos, Kyriakos P., Padda, Sukhmani K., Shah, Sumit A., Colevas, A Dimitrios, Narayanan, Sujata, Fisher, George A., Supan, Dana, Wakelee, Heather A., Aoki, Rhonda, Pegram, Mark D., Villalobos, Victor M., Liu, Jie, Takimoto, Chris H., Chao, Mark, Volkmer, Jens-Peter, Majeti, Ravindra, Weissman, Irving L., Sikic, Branimir I., Yu, Wendy, Conlin, Alison, Ruzich, Janet, Lewis, Stacy, Acheson, Anupama, Kemmer, Kathleen, Perlewitz, Kelly, Moxon, Nicole M., Mellinger, Staci, McArthur, Heather, Juhler-Nøttrup, Trine, Desai, Jayesh, Markman, Ben, Sandhu, Shahneen, Gan, Hui, Friedlander, Michael L., Tran, Ben, Meniawy, Tarek, Lundy, Joanne, Colyer, Duncan, Ameratunga, Malaka, Norris, Christie, Yang, Jason, Li, Kang, Wang, Lai, Luo, Lusong, Qin, Zhen, Mu, Song, Tan, Xuemei, Song, James, Millward, Michael, Katz, Matthew H. G., Bauer, Todd W., Varadhachary, Gauri R., Acquavella, Nicolas, Merchant, Nipun, Petroni, Gina, Rahma, Osama E., Chen, Mei, Song, Yang, Puhlmann, Markus, Khattri, Arun, Brisson, Ryan, Harvey, Christopher, Shah, Jatin, Mateos, Maria Victoria, Matsumoto, Morio, Blacklock, Hilary, Rocafiguera, Albert Oriol, Goldschmidt, Hartmut, Iida, Shinsuke, Yehuda, Dina Ben, Ocio, Enrique, Rodríguez-Otero, Paula, Jagannath, Sundar, Lonial, Sagar, Kher, Uma, San-Miguel, Jesus, de Oliveira, Moacyr Ribeiro, Yimer, Habte, Rifkin, Robert, Schjesvold, Fredrik, Ghori, Razi, Spreafico, Anna, Lee, Victor, Ngan, Roger K. C., To, Ka Fai, Ahn, Myung Ju, Ng, Quan Sing, Lin, Jin-Ching, Swaby, Ramona F., Gause, Christine, Saraf, Sanatan, Chan, Anthony T. C., Lam, Elaine, Tannir, Nizar M., Meric-Bernstam, Funda, Gross, Matt, MacKinnon, Andy, Whiting, Sam, Voss, Martin, Yu, Evan Y., Albertini, Mark R., Ranheim, Erik A., Hank, Jacquelyn A., Zuleger, Cindy, McFarland, Thomas, Collins, Jennifer, Clements, Erin, Weber, Sharon, Weigel, Tracey, Neuman, Heather, Hartig, Greg, Mahvi, David, Henry, MaryBeth, Gan, Jacek, Yang, Richard, Carmichael, Lakeesha, Kim, KyungMann, Gillies, Stephen D., Sondel, Paul M., Subbiah, Vivek, Noffsinger, Lori, Hendricks, Kyle, Bosch, Marnix, Lee, Jay M., Lee, Mi-Heon, Goldman, Jonathan W., Baratelli, Felicita E., Schaue, Dorthe, Wang, Gerald, Rosen, Frances, Yanagawa, Jane, Walser, Tonya C., Lin, Ying Q., Adams, Sharon, Marincola, Franco M., Tumeh, Paul C., Abtin, Fereidoun, Suh, Robert, Reckamp, Karen, Wallace, William D., Zeng, Gang, Elashoff, David A., Sharma, Sherven, Dubinett, Steven M., Pavlick, Anna C., Gastman, Brian, Hanks, Brent, Keler, Tibor, Davis, Tom, Vitale, Laura A., Sharon, Elad, Morishima, Chihiro, Cheever, Martin, Heery, Christopher R., Kim, Joseph W., Lamping, Elizabeth, Marte, Jennifer, McMahon, Sheri, Cordes, Lisa, Fakhrejahani, Farhad, Madan, Ravi, Salazar, Rachel, Zhang, Maggie, Helwig, Christoph, Gulley, James L, Li, Roger, Amrhein, John, Cohen, Zvi, Champagne, Monique, Kamat, Ashish, Aznar, M. Angela, Labiano, Sara, Diaz-Lagares, Angel, Esteller, Manel, Sandoval, Juan, Barbee, Susannah D., Bellovin, David I., Timmer, John C., Wondyfraw, Nebiyu, Johnson, Susan, Park, Johanna, Chen, Amanda, Mkrtichyan, Mikayel, Razai, Amir S., Jones, Kyle S., Hata, Chelsie Y., Gonzalez, Denise, Deveraux, Quinn, Eckelman, Brendan P., Borges, Luis, Bhardwaj, Rukmini, Puri, Raj K., Suzuki, Akiko, Leland, Pamela, Joshi, Bharat H., Bartkowiak, Todd, Jaiswal, Ashvin, Ager, Casey, Ai, Midan, Budhani, Pratha, Chin, Renee, Hong, David, Curran, Michael, Hastings, William D., Pinzon-Ortiz, Maria, Murakami, Masato, Dobson, Jason R., Quinn, David, Wagner, Joel P., Rong, Xianhui, Shaw, Pamela, Dammassa, Ernesta, Guan, Wei, Dranoff, Glenn, Cao, Alexander, Fulton, Ross B., Leonardo, Steven, Fraser, Kathryn, Kangas, Takashi O., Ottoson, Nadine, Bose, Nandita, Huhn, Richard D., Graff, Jeremy, Lowe, Jamie, Gorden, Keith, Uhlik, Mark, O’Neill, Thomas, Widger, Jenifer, Crocker, Andrea, He, Li-Zhen, Weidlick, Jeffrey, Sundarapandiyan, Karuna, Ramakrishna, Venky, Storey, James, Thomas, Lawrence J., Goldstein, Joel, Marsh, Henry C., Grailer, Jamison, Gilden, Julia, Stecha, Pete, Garvin, Denise, Hartnett, Jim, Fan, Frank, Cong, Mei, Cheng, Zhi-jie Jey, Hinner, Marlon J., Aiba, Rachida-Siham Bel, Schlosser, Corinna, Jaquin, Thomas, Allersdorfer, Andrea, Berger, Sven, Wiedenmann, Alexander, Matschiner, Gabriele, Schüler, Julia, Moebius, Ulrich, Rothe, Christine, Shane, Olwill A., Horton, Brendan, Spranger, Stefani, Moreira, Dayson, Adamus, Tomasz, Zhao, Xingli, Swiderski, Piotr, Pal, Sumanta, Kortylewski, Marcin, Kosmides, Alyssa, Necochea, Kevin, Mahoney, Kathleen M., Shukla, Sachet A., Patsoukis, Nikolaos, Chaudhri, Apoorvi, Pham, Hung, Hua, Ping, Bu, Xia, Zhu, Baogong, Hacohen, Nir, Wu, Catherine J., Fritsch, Edward, Boussiotis, Vassiliki A., Freeman, Gordon J., Moran, Amy E., Polesso, Fanny, Lukaesko, Lisa, Rådestad, Emelie, Egevad, Lars, Sundberg, Berit, Henningsohn, Lars, Levitsky, Victor, Rafelson, William, Reagan, John L., Fast, Loren, Sasikumar, Pottayil, Sudarshan, Naremaddepalli, Ramachandra, Raghuveer, Gowda, Nagesh, Samiulla, Dodheri, Chandrasekhar, Talapaneni, Adurthi, Sreenivas, Mani, Jiju, Nair, Rashmi, Dhudashia, Amit, Gowda, Nagaraj, Ramachandra, Murali, Sankin, Alexander, Gartrell, Benjamin, Cumberbatch, Kerwin, Huang, Hongying, Stern, Joshua, Schoenberg, Mark, Zang, Xingxing, Swanson, Ryan, Kornacker, Michael, Evans, Lawrence, Rickel, Erika, Wolfson, Martin, Valsesia-Wittmann, Sandrine, Shekarian, Tala, Simard, François, Nailo, Rodrigo, Dutour, Aurélie, Jallas, Anne-Catherine, Caux, Christophe, and Marabelle, Aurélien

Published
2016
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37. CD4+T Cells Recognize Conserved Influenza A Epitopes through Shared Patterns of V-Gene Usage and Complementary Biochemical Features

Author

Greenshields-Watson, Alexander, Attaf, Meriem, MacLachlan, Bruce J., Whalley, Thomas, Rius, Cristina, Wall, Aaron, Lloyd, Angharad, Hughes, Hywel, Strange, Kathryn E., Mason, Georgina H., Schauenburg, Andrea J., Hulin-Curtis, Sarah L., Geary, James, Chen, Yuan, Lauder, Sarah N., Smart, Kathryn, Vijaykrishna, Dhanasekaran, Grau, Miguel L., Shugay, Mikhail, Andrews, Robert, Dolton, Garry, Rizkallah, Pierre J., Gallimore, Awen M., Sewell, Andrew K., Godkin, Andrew J., and Cole, David K.

Abstract

T cell recognition of peptides presented by human leukocyte antigens (HLAs) is mediated by the highly variable T cell receptor (TCR). Despite this built-in TCR variability, individuals can mount immune responses against viral epitopes by using identical or highly related TCRs expressed on CD8+T cells. Characterization of these TCRs has extended our understanding of the molecular mechanisms that govern the recognition of peptide-HLA. However, few examples exist for CD4+T cells. Here, we investigate CD4+T cell responses to the internal proteins of the influenza A virus that correlate with protective immunity. We identify five internal epitopes that are commonly recognized by CD4+T cells in five HLA-DR1+subjects and show conservation across viral strains and zoonotic reservoirs. TCR repertoire analysis demonstrates several shared gene usage biases underpinned by complementary biochemical features evident in a structural comparison. These epitopes are attractive targets for vaccination and other T cell therapies.

Published
2020
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38. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one

Author

Lundqvist, Andreas, van Hoef, Vincent, Zhang, Xiaonan, Wennerberg, Erik, Lorent, Julie, Witt, Kristina, Sanz, Laia Masvidal, Liang, Shuo, Murray, Shannon, Larsson, Ola, Kiessling, Rolf, Mao, Yumeng, Sidhom, John-William, Bessell, Catherine A., Havel, Jonathan, Schneck, Jonathan, Chan, Timothy A., Sachsenmeier, Eliot, Woods, David, Berglund, Anders, Ramakrishnan, Rupal, Sodre, Andressa, Weber, Jeffrey, Zappasodi, Roberta, Li, Yanyun, Qi, Jingjing, Wong, Philip, Sirard, Cynthia, Postow, Michael, Newman, Walter, Koon, Henry, Velcheti, Vamsidhar, Callahan, Margaret K., Wolchok, Jedd D., Merghoub, Taha, Lum, Lawrence G., Choi, Minsig, Thakur, Archana, Deol, Abhinav, Dyson, Gregory, Shields, Anthony, Haymaker, Cara, Uemura, Marc, Murthy, Ravi, James, Marihella, Wang, Daqing, Brevard, Julie, Monaghan, Catherine, Swann, Suzanne, Geib, James, Cornfeld, Mark, Chunduru, Srinivas, Agrawal, Sudhir, Yee, Cassian, Wargo, Jennifer, Patel, Sapna P., Amaria, Rodabe, Tawbi, Hussein, Glitza, Isabella, Woodman, Scott, Hwu, Wen-Jen, Davies, Michael A., Hwu, Patrick, Overwijk, Willem W., Bernatchez, Chantale, Diab, Adi, Massarelli, Erminia, Segal, Neil H., Ribrag, Vincent, Melero, Ignacio, Gangadhar, Tara C., Urba, Walter, Schadendorf, Dirk, Ferris, Robert L., Houot, Roch, Morschhauser, Franck, Logan, Theodore, Luke, Jason J., Sharfman, William, Barlesi, Fabrice, Ott, Patrick A., Mansi, Laura, Kummar, Shivaani, Salles, Gilles, Carpio, Cecilia, Meier, Roland, Krishnan, Suba, McDonald, Dan, Maurer, Matthew, Gu, Xuemin, Neely, Jaclyn, Suryawanshi, Satyendra, Levy, Ronald, Khushalani, Nikhil, Wu, Jennifer, Zhang, Jinyu, Basher, Fahmin, Rubinstein, Mark, Bucsek, Mark, Qiao, Guanxi, MacDonald, Cameron, Hylander, Bonnie, Repasky, Elizabeth, Chatterjee, Shilpak, Daenthanasanmak, Anusara, Chakraborty, Paramita, Toth, Kyle, Meek, Megan, Garrett-Mayer, Elizabeth, Nishimura, Michael, Paulos, Chrystal, Beeson, Craig, Yu, Xuezhong, Mehrotra, Shikhar, Zhao, Fei, Evans, Kathy, Xiao, Christine, Holtzhausen, Alisha, Hanks, Brent A., Scharping, Nicole, Menk, Ashley V., Moreci, Rebecca, Whetstone, Ryan, Dadey, Rebekah, Watkins, Simon, Ferris, Robert, Delgoffe, Greg M., Peled, Jonathan, Devlin, Sean, Staffas, Anna, Lumish, Melissa, Rodriguez, Kori Porosnicu, Ahr, Katya, Perales, Miguel, Giralt, Sergio, Taur, Ying, Pamer, Eric, van den Brink, Marcel R. M., Jenq, Robert, Annels, Nicola, Pandha, Hardev, Simpson, Guy, Mostafid, Hugh, Harrington, Kevin, Melcher, Alan, Grose, Mark, Davies, Bronwyn, Au, Gough, Karpathy, Roberta, Shafren, Darren, Ricca, Jacob, Zamarin, Dmitriy, Batista, Luciana, Marliot, Florence, Vasaturo, Angela, Carpentier, Sabrina, Poggionovo, Cécile, Frayssinet, Véronique, Fieschi, Jacques, Van den Eynde, Marc, Pagès, Franck, Galon, Jérôme, Hermitte, Fabienne, Smith, Sean G., Nguyen, Khue, Ravindranathan, Sruthi, Koppolu, Bhanu, Zaharoff, David, Schvartsman, Gustavo, Bassett, Roland, McQuade, Jennifer L., Haydu, Lauren E., Kline, Douglas, Chen, Xiufen, Fosco, Dominick, Kline, Justin, Overacre, Abigail, Chikina, Maria, Brunazzi, Erin, Shayan, Gulidanna, Horne, William, Kolls, Jay, Bruno, Tullia C., Workman, Creg, Vignali, Dario, Adusumilli, Prasad S., Ansa-Addo, Ephraim A, Li, Zihai, Gerry, Andrew, Sanderson, Joseph P., Howe, Karen, Docta, Roslin, Gao, Qian, Bagg, Eleanor A. L., Tribble, Nicholas, Maroto, Miguel, Betts, Gareth, Bath, Natalie, Melchiori, Luca, Lowther, Daniel E., Ramachandran, Indu, Kari, Gabor, Basu, Samik, Binder-Scholl, Gwendolyn, Chagin, Karen, Pandite, Lini, Holdich, Tom, Amado, Rafael, Zhang, Hua, Glod, John, Bernstein, Donna, Jakobsen, Bent, Mackall, Crystal, Wong, Ryan, Silk, Jonathan D., Adams, Katherine, Hamilton, Garth, Bennett, Alan D., Brett, Sara, Jing, Junping, Quattrini, Adriano, Saini, Manoj, Wiedermann, Guy, Brewer, Joanna, Duong, MyLinh, Lu, An, Chang, Peter, Mahendravada, Aruna, Shinners, Nicholas, Slawin, Kevin, Spencer, David M., Foster, Aaron E., Bayle, J. Henri, Bergamaschi, Cristina, Ng, Sinnie Sin Man, Nagy, Bethany, Jensen, Shawn, Hu, Xintao, Alicea, Candido, Fox, Bernard, Felber, Barbara, Pavlakis, George, Chacon, Jessica, Yamamoto, Tori, Garrabrant, Thomas, Cortina, Luis, Powell, Daniel J., Donia, Marco, Kjeldsen, Julie Westerlin, Andersen, Rikke, Westergaard, Marie Christine Wulff, Bianchi, Valentina, Legut, Mateusz, Attaf, Meriem, Dolton, Garry, Szomolay, Barbara, Ott, Sascha, Lyngaa, Rikke, Hadrup, Sine Reker, Sewell, Andrew Kelvin, Svane, Inge Marie, Fan, Aaron, Kumai, Takumi, Celis, Esteban, Frank, Ian, Stramer, Amanda, Blaskovich, Michelle A., Wardell, Seth, Fardis, Maria, Bender, James, Lotze, Michael T., Goff, Stephanie L., Zacharakis, Nikolaos, Assadipour, Yasmine, Prickett, Todd D., Gartner, Jared J., Somerville, Robert, Black, Mary, Xu, Hui, Chinnasamy, Harshini, Kriley, Isaac, Lu, Lily, Wunderlich, John, Robbins, Paul F., Rosenberg, Steven, Feldman, Steven A., Trebska-McGowan, Kasia, Malekzadeh, Parisa, Payabyab, Eden, Sherry, Richard, Gokuldass, Aishwarya, Kopits, Charlene, Rabinovich, Brian, Green, Daniel S., Kamenyeva, Olena, Zoon, Kathryn C., Annunziata, Christina M., Hammill, Joanne, Helsen, Christopher, Aarts, Craig, Bramson, Jonathan, Harada, Yui, Yonemitsu, Yoshikazu, Mwawasi, Kenneth, Denisova, Galina, Giri, Rajanish, Jin, Benjamin, Campbell, Tracy, Draper, Lindsey M., Stevanovic, Sanja, Yu, Zhiya, Weissbrich, Bianca, Restifo, Nicholas P., Trimble, Cornelia L., Hinrichs, Christian S., Tsang, Kwong, Fantini, Massimo, Hodge, James W., Fujii, Rika, Fernando, Ingrid, Jochems, Caroline, Heery, Christopher, Gulley, James, Soon-Shiong, Patrick, Schlom, Jeffrey, Jing, Weiqing, Gershan, Jill, Blitzer, Grace, Weber, James, McOlash, Laura, Johnson, Bryon D., Kiany, Simin, Gangxiong, Huang, Kleinerman, Eugenie S., Klichinsky, Michael, Ruella, Marco, Shestova, Olga, Kenderian, Saad, Kim, Miriam, Scholler, John, June, Carl H., Gill, Saar, Moogk, Duane, Zhong, Shi, Liadi, Ivan, Rittase, William, Fang, Victoria, Dougherty, Janna, Perez-Garcia, Arianne, Osman, Iman, Zhu, Cheng, Varadarajan, Navin, Frey, Alan, Krogsgaard, Michelle, Landi, Daniel, Fousek, Kristen, Mukherjee, Malini, Shree, Ankita, Joseph, Sujith, Bielamowicz, Kevin, Byrd, Tiara, Ahmed, Nabil, Hegde, Meenakshi, Lee, Sylvia, Byrd, David, Thompson, John, Bhatia, Shailender, Tykodi, Scott, Delismon, Judy, Chu, Liz, Abdul-Alim, Siddiq, Ohanian, Arpy, DeVito, Anna Marie, Riddell, Stanley, Margolin, Kim, Magalhaes, Isabelle, Mattsson, Jonas, Uhlin, Michael, Nemoto, Satoshi, Villarroel, Patricio Pérez, Nakagawa, Ryosuke, Mule, James J., Mailloux, Adam W., Mata, Melinda, Nguyen, Phuong, Gerken, Claudia, DeRenzo, Christopher, Gottschalk, Stephen, Mathieu, Mélissa, Pelletier, Sandy, Stagg, John, Turcotte, Simon, Minutolo, Nicholas, Sharma, Prannda, Tsourkas, Andrew, Mockel-Tenbrinck, Nadine, Mauer, Daniela, Drechsel, Katharina, Barth, Carola, Freese, Katharina, Kolrep, Ulrike, Schult, Silke, Assenmacher, Mario, Kaiser, Andrew, Mullinax, John, Hall, MacLean, Le, Julie, Kodumudi, Krithika, Royster, Erica, Richards, Allison, Gonzalez, Ricardo, Sarnaik, Amod, Pilon-Thomas, Shari, Nielsen, Morten, Krarup-Hansen, Anders, Hovgaard, Dorrit, Petersen, Michael Mørk, Loya, Anand Chainsukh, Junker, Niels, Rivas, Charlotte, Parihar, Robin, Rooney, Cliona M., Qin, Haiying, Nguyen, Sang, Su, Paul, Burk, Chad, Duncan, Brynn, Kim, Bong-Hyun, Kohler, M. 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David, Tsai, Katy, Nosrati, Adi, Goldinger, Simone, Hamid, Omid, Algazi, Alain, Tumeh, Paul, Hwang, Jimmy, Liu, Jacqueline, Chen, Lawrence, Dummer, Reinhard, Rosenblum, Michael, Daud, Adil, Tsao, Tsu-Shuen, Ashworth-Sharpe, Julia, Johnson, Donald, Bhaumik, Srabani, Bieniarz, Christopher, Couto, Joseph, Farrell, Michael, Ghaffari, Mahsa, Hubbard, Antony, Kosmeder, Jerome, Lee, Cleo, Marner, Erin, Uribe, Diana, Zhang, Hongjun, Zhang, Jian, Zhang, Wenjun, Zhu, Yifei, Morrison, Larry, Tsujikawa, Takahiro, Borkar, Rohan N., Azimi, Vahid, Kumar, Sushil, Thibault, Guillaume, Mori, Motomi, El Rassi, Edward, Clayburgh, Daniel R., Kulesz-Martin, Molly F., Flint, Paul W., Coussens, Lisa M., Villabona, Lisa, Masucci, Giuseppe V., Geiss, Gary, Birditt, Brian, Mei, Qian, Huang, Alan, Eagan, Maribeth A., Ignacio, Eduardo, Elliott, Nathan, Dunaway, Dwayne, Jung, Jaemyeong, Merritt, Chris, Sprague, Isaac, Webster, Philippa, Liang, Yan, Wenthe, Jessica, Enblad, Gunilla, Karlsson, Hannah, Essand, Magnus, Savoldo, Barbara, Dotti, Gianpietro, Höglund, Martin, Brenner, Malcolm K., Hagberg, Hans, Loskog, Angelica, Bernett, Matthew J., Moore, Gregory L., Hedvat, Michael, Bonzon, Christine, Chu, Seung, Rashid, Rumana, Avery, Kendra N., Muchhal, Umesh, Desjarlais, John, Kraman, Matthew, Kmiecik, Katarzyna, Allen, Natalie, Faroudi, Mustapha, Zimarino, Carlo, Wydro, Mateusz, Doody, Jacqueline, Srinivasa, Sreesha P., Govindappa, Nagaraja, Reddy, Praveen, Dubey, Aparajita, Periyasamy, Sankar, Adekandi, Madhukara, Dey, Chaitali, Joy, Mary, van Loo, Pieter Fokko, Veninga, Henrike, Shamsili, Setareh, Throsby, Mark, Dolstra, Harry, Bakker, Lex, Alva, Ajjai, Gschwendt, Juergen, Loriot, Yohann, Bellmunt, Joaquim, Feng, Dai, Poehlein, Christian, Powles, Thomas, Antonarakis, Emmanuel S., Drake, Charles G., Wu, Haiyan, De Bono, Johann, Bannerji, Rajat, Byrd, John, Gregory, Gareth, Opat, Stephen, Shortt, Jake, Yee, Andrew J., Raje, Noopur, Thompson, Seth, Balakumaran, Arun, Kumar, Shaji, Rini, Brian I., Choueiri, Toni K., Mariani, Mariangela, Albiges, Laurence, Haanen, John B., Larkin, James, Schmidinger, Manuela, Magazzù, Domenico, di Pietro, Alessandra, Motzer, Robert J., Borch, Troels Holz, Kongsted, Per, Pedersen, Magnus, Met, Özcan, Boudadi, Karim, Wang, Hao, Vasselli, James, Baughman, Jan E., Wigginton, Jon, Abdallah, Rehab, Ross, Ashley, Park, Jiwon, Grossenbacher, Steven, Luna, Jesus I., Withers, Sita, Culp, William, Chen, Mingyi, Monjazeb, Arta, Kent, Michael S., Chandran, Smita, Danforth, David, Yang, James, Klebanoff, Christopher, Goff, Stephanie, Paria, Biman, Sabesan, Arvind, Srivastava, Abhishek, Kammula, Udai, Richards, Jon, Faries, Mark, Andtbacka, Robert H. I., Diaz, Luis A., Le, Dung T., Yoshino, Takayuki, André, Thierry, Bendell, Johanna, Koshiji, Minori, Zhang, Yayan, Kang, S Peter, Lam, Bao, Jäger, Dirk, Bauer, Todd M., Wang, Judy S., Lee, Jean K., Manji, Gulam A., Kudchadkar, Ragini, Kauh, John S., Tang, Shande, Laing, Naomi, Falchook, Gerald, Garon, Edward B., Halmos, Balazs, Rina, Hui, Leighl, Natasha, Lee, Sung Sook, Walsh, William, Dragnev, Konstanin, Piperdi, Bilal, Rodriguez, Luis Paz-Ares, Shinwari, Nabeegha, Wei, Ziewn, Maas, Mary L, Deeds, Michael, Armstrong, Adam, Peterson, Tim, Steinmetz, Sue, Herzog, Thomas, Backes, Floor J., Copeland, Larry, Del Pilar Estevez Diz, Maria, Hare, Thomas W., Huh, Warner, Kim, Byoung-Gie, Moore, Kathleen M., Oaknin, Ana, Small, William, Tewari, Krishnansu S., Monk, Bradley J., Kamat, Ashish M., Nam, Kijoeng, De Santis, Maria, Dreicer, Robert, Hahn, Noah M., Perini, Rodolfo, Siefker-Radtke, Arlene, Sonpavde, Guru, de Wit, Ronald, Witjes, J. Alfred, Keefe, Stephen, Bajorin, Dean, Armand, Philippe, Kuruvilla, John, Moskowitz, Craig, Hamadani, Mehdi, Zinzani, Pier Luigi, Chlosta, Sabine, Bartlett, Nancy, Sabado, Rachel, Saenger, Yvonne, William, Loging, Donovan, Michael Joseph, Sacris, Erlinda, Mandeli, John, Salazar, Andres M., Powderly, John, Brody, Joshua, Nemunaitis, John, Emens, Leisha, Patnaik, Amita, McCaffery, Ian, Miller, Richard, Laport, Ginna, Coveler, Andrew L., Smith, David C., Grilley-Olson, Juneko E., Goel, Sanjay, Gardai, Shyra J., Law, Che-Leung, Means, Gary, Manley, Thomas, Marrone, Kristen A., Rosner, Gary, Anagnostou, Valsamo, Riemer, Joanne, Wakefield, Jessica, Zanhow, Cynthia, Baylin, Stephen, Gitlitz, Barbara, Brahmer, Julie, Signoretti, Sabina, Li, Wenting, Schloss, Charles, Michot, Jean-Marie, Ding, Wei, Christian, Beth, Marinello, Patricia, Shipp, Margaret, Najjar, Yana G., Lin, Butterfield, Lisa H., Tarhini, Ahmad A., Davar, Diwakar, Zarour, Hassane, Rush, Elizabeth, Sander, Cindy, Fu, Siqing, Bauer, Todd, Molineaux, Chris, Bennett, Mark K., Orford, Keith W., Papadopoulos, Kyriakos P., Padda, Sukhmani K., Shah, Sumit A., Colevas, A Dimitrios, Narayanan, Sujata, Fisher, George A., Supan, Dana, Wakelee, Heather A., Aoki, Rhonda, Pegram, Mark D., Villalobos, Victor M., Liu, Jie, Takimoto, Chris H., Chao, Mark, Volkmer, Jens-Peter, Majeti, Ravindra, Weissman, Irving L., Sikic, Branimir I., Yu, Wendy, Conlin, Alison, Ruzich, Janet, Lewis, Stacy, Acheson, Anupama, Kemmer, Kathleen, Perlewitz, Kelly, Moxon, Nicole M., Mellinger, Staci, McArthur, Heather, Juhler-Nøttrup, Trine, Desai, Jayesh, Markman, Ben, Sandhu, Shahneen, Gan, Hui, Friedlander, Michael L., Tran, Ben, Meniawy, Tarek, Lundy, Joanne, Colyer, Duncan, Ameratunga, Malaka, Norris, Christie, Yang, Jason, Li, Kang, Wang, Lai, Luo, Lusong, Qin, Zhen, Mu, Song, Tan, Xuemei, Song, James, Millward, Michael, Katz, Matthew H. G., Bauer, Todd W., Varadhachary, Gauri R., Acquavella, Nicolas, Merchant, Nipun, Petroni, Gina, Rahma, Osama E., Chen, Mei, Song, Yang, Puhlmann, Markus, Khattri, Arun, Brisson, Ryan, Harvey, Christopher, Shah, Jatin, Mateos, Maria Victoria, Matsumoto, Morio, Blacklock, Hilary, Rocafiguera, Albert Oriol, Goldschmidt, Hartmut, Iida, Shinsuke, Yehuda, Dina Ben, Ocio, Enrique, Rodríguez-Otero, Paula, Jagannath, Sundar, Lonial, Sagar, Kher, Uma, San-Miguel, Jesus, de Oliveira, Moacyr Ribeiro, Yimer, Habte, Rifkin, Robert, Schjesvold, Fredrik, Ghori, Razi, Spreafico, Anna, Lee, Victor, Ngan, Roger K. C., To, Ka Fai, Ahn, Myung Ju, Ng, Quan Sing, Lin, Jin-Ching, Swaby, Ramona F., Gause, Christine, Saraf, Sanatan, Chan, Anthony T. C., Lam, Elaine, Tannir, Nizar M., Meric-Bernstam, Funda, Gross, Matt, MacKinnon, Andy, Whiting, Sam, Voss, Martin, Yu, Evan Y., Albertini, Mark R., Ranheim, Erik A., Hank, Jacquelyn A., Zuleger, Cindy, McFarland, Thomas, Collins, Jennifer, Clements, Erin, Weber, Sharon, Weigel, Tracey, Neuman, Heather, Hartig, Greg, Mahvi, David, Henry, MaryBeth, Gan, Jacek, Yang, Richard, Carmichael, Lakeesha, Kim, KyungMann, Gillies, Stephen D., Sondel, Paul M., Subbiah, Vivek, Noffsinger, Lori, Hendricks, Kyle, Bosch, Marnix, Lee, Jay M., Lee, Mi-Heon, Goldman, Jonathan W., Baratelli, Felicita E., Schaue, Dorthe, Wang, Gerald, Rosen, Frances, Yanagawa, Jane, Walser, Tonya C., Lin, Ying Q., Adams, Sharon, Marincola, Franco M., Tumeh, Paul C., Abtin, Fereidoun, Suh, Robert, Reckamp, Karen, Wallace, William D., Zeng, Gang, Elashoff, David A., Sharma, Sherven, Dubinett, Steven M., Pavlick, Anna C., Gastman, Brian, Hanks, Brent, Keler, Tibor, Davis, Tom, Vitale, Laura A., Sharon, Elad, Morishima, Chihiro, Cheever, Martin, Heery, Christopher R., Kim, Joseph W., Lamping, Elizabeth, Marte, Jennifer, McMahon, Sheri, Cordes, Lisa, Fakhrejahani, Farhad, Madan, Ravi, Salazar, Rachel, Zhang, Maggie, Helwig, Christoph, Gulley, James L, Li, Roger, Amrhein, John, Cohen, Zvi, Champagne, Monique, Kamat, Ashish, Aznar, M. Angela, Labiano, Sara, Diaz-Lagares, Angel, Esteller, Manel, Sandoval, Juan, Barbee, Susannah D., Bellovin, David I., Timmer, John C., Wondyfraw, Nebiyu, Johnson, Susan, Park, Johanna, Chen, Amanda, Mkrtichyan, Mikayel, Razai, Amir S., Jones, Kyle S., Hata, Chelsie Y., Gonzalez, Denise, Deveraux, Quinn, Eckelman, Brendan P., Borges, Luis, Bhardwaj, Rukmini, Puri, Raj K., Suzuki, Akiko, Leland, Pamela, Joshi, Bharat H., Bartkowiak, Todd, Jaiswal, Ashvin, Ager, Casey, Ai, Midan, Budhani, Pratha, Chin, Renee, Hong, David, Curran, Michael, Hastings, William D., Pinzon-Ortiz, Maria, Murakami, Masato, Dobson, Jason R., Quinn, David, Wagner, Joel P., Rong, Xianhui, Shaw, Pamela, Dammassa, Ernesta, Guan, Wei, Dranoff, Glenn, Cao, Alexander, Fulton, Ross B., Leonardo, Steven, Fraser, Kathryn, Kangas, Takashi O., Ottoson, Nadine, Bose, Nandita, Huhn, Richard D., Graff, Jeremy, Lowe, Jamie, Gorden, Keith, Uhlik, Mark, O’Neill, Thomas, Widger, Jenifer, Crocker, Andrea, He, Li-Zhen, Weidlick, Jeffrey, Sundarapandiyan, Karuna, Ramakrishna, Venky, Storey, James, Thomas, Lawrence J., Goldstein, Joel, Marsh, Henry C., Grailer, Jamison, Gilden, Julia, Stecha, Pete, Garvin, Denise, Hartnett, Jim, Fan, Frank, Cong, Mei, Cheng, Zhi-jie Jey, Hinner, Marlon J., Aiba, Rachida-Siham Bel, Schlosser, Corinna, Jaquin, Thomas, Allersdorfer, Andrea, Berger, Sven, Wiedenmann, Alexander, Matschiner, Gabriele, Schüler, Julia, Moebius, Ulrich, Rothe, Christine, Shane, Olwill A., Horton, Brendan, Spranger, Stefani, Moreira, Dayson, Adamus, Tomasz, Zhao, Xingli, Swiderski, Piotr, Pal, Sumanta, Kortylewski, Marcin, Kosmides, Alyssa, Necochea, Kevin, Mahoney, Kathleen M., Shukla, Sachet A., Patsoukis, Nikolaos, Chaudhri, Apoorvi, Pham, Hung, Hua, Ping, Bu, Xia, Zhu, Baogong, Hacohen, Nir, Wu, Catherine J., Fritsch, Edward, Boussiotis, Vassiliki A., Freeman, Gordon J., Moran, Amy E., Polesso, Fanny, Lukaesko, Lisa, Rådestad, Emelie, Egevad, Lars, Sundberg, Berit, Henningsohn, Lars, Levitsky, Victor, Rafelson, William, Reagan, John L., Fast, Loren, Sasikumar, Pottayil, Sudarshan, Naremaddepalli, Ramachandra, Raghuveer, Gowda, Nagesh, Samiulla, Dodheri, Chandrasekhar, Talapaneni, Adurthi, Sreenivas, Mani, Jiju, Nair, Rashmi, Dhudashia, Amit, Gowda, Nagaraj, Ramachandra, Murali, Sankin, Alexander, Gartrell, Benjamin, Cumberbatch, Kerwin, Huang, Hongying, Stern, Joshua, Schoenberg, Mark, Zang, Xingxing, Swanson, Ryan, Kornacker, Michael, Evans, Lawrence, Rickel, Erika, Wolfson, Martin, Valsesia-Wittmann, Sandrine, Shekarian, Tala, Simard, François, Nailo, Rodrigo, Dutour, Aurélie, Jallas, Anne-Catherine, Caux, Christophe, and Marabelle, Aurélien

Subjects
Meeting Abstracts
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39. The T-cell receptor is not hardwired to engage MHC ligands.

Author

HoIIand, Stephen J., Bartok, lstvan, Attaf, Meriem, Genolet, Raphael, Luescher, Immanuel F., Kotsiou, Eleni, Richard, Ashkenaz, Wang, Edward, White, Matthew, Coe, David J., Jian-Guo Chai, Ferreira, Cristina, and Dyson, Julian

Subjects
CELL receptors, MAJOR histocompatibility complex, INTERLEUKIN-2, B cells, CELLULAR immunity
Abstract

The article presents a study which discusses how the T-cell receptor (TCR) and the B-cell receptor (BCR) bind to a vast range of major histocompatibility complex (MHC) molecules. It examines the antigen recognition used by the TCR and the BCR in understanding the evolution of adaptive immunity. It investigates the requirement of the TCR for engagement with MHC class l and ll molecules.

Published
2012
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40. VDJdb in 2019: database extension, new analysis infrastructure and a T-cell receptor motif compendium.

Author

Bagaev DV, Vroomans RMA, Samir J, Stervbo U, Rius C, Dolton G, Greenshields-Watson A, Attaf M, Egorov ES, Zvyagin IV, Babel N, Cole DK, Godkin AJ, Sewell AK, Kesmir C, Chudakov DM, Luciani F, and Shugay M

Subjects
Amino Acid Sequence, High-Throughput Nucleotide Sequencing, Humans, Position-Specific Scoring Matrices, Receptors, Antigen, T-Cell chemistry, Sequence Analysis, DNA, Software, Web Browser, Computational Biology methods, Databases, Genetic, Nucleotide Motifs, Receptors, Antigen, T-Cell genetics, V(D)J Recombination
Abstract

Here, we report an update of the VDJdb database with a substantial increase in the number of T-cell receptor (TCR) sequences and their cognate antigens. The update further provides a new database infrastructure featuring two additional analysis modes that facilitate database querying and real-world data analysis. The increased yield of TCR specificity identification methods and the overall increase in the number of studies in the field has allowed us to expand the database more than 5-fold. Furthermore, several new analysis methods are included. For example, batch annotation of TCR repertoire sequencing samples allows for annotating large datasets on-line. Using recently developed bioinformatic methods for TCR motif mining, we have built a reduced set of high-quality TCR motifs that can be used for both training TCR specificity predictors and matching against TCRs of interest. These additions enhance the versatility of the VDJdb in the task of exploring T-cell antigen specificities. The database is available at https://vdjdb.cdr3.net., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Published
2020
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41. Major TCR Repertoire Perturbation by Immunodominant HLA-B * 44:03-Restricted CMV-Specific T Cells.

Author

Attaf M, Malik A, Severinsen MC, Roider J, Ogongo P, Buus S, Ndung'u T, Leslie A, Kløverpris HN, Matthews PC, Sewell AK, and Goulder P

Subjects
Adult, Epitopes, T-Lymphocyte immunology, Flow Cytometry, HLA-B44 Antigen metabolism, High-Throughput Nucleotide Sequencing, Humans, Immediate-Early Proteins genetics, Immediate-Early Proteins immunology, Immunity, Cellular, Immunodominant Epitopes immunology, Male, Peptides genetics, Peptides immunology, South Africa, Trans-Activators genetics, Trans-Activators immunology, Young Adult, Black People, CD8-Positive T-Lymphocytes physiology, Cytomegalovirus physiology, Cytomegalovirus Infections immunology, Receptors, Antigen, T-Cell genetics
Abstract

Lack of disease during chronic human cytomegalovirus (CMV) infection depends on the maintenance of a high-frequency CMV-specific T cell response. The composition of the T cell receptor (TCR) repertoire underlying this response remains poorly characterised, especially within African populations in which CMV is endemic from infancy. Here we focus on the immunodominant CD8+ T cell response to the immediate-early 2 (IE-2)-derived epitope NEGVKAAW (NW8) restricted by HLA-B * 44:03, a highly prevalent response in African populations, which in some subjects represents >10% of the circulating CD8+ T cells. Using pMHC multimer staining and sorting of NW8-specific T cells, the TCR repertoire raised against NW8 was characterised here using high-throughput sequencing in 20 HLA-B * 44:03 subjects. We found that the CD8+ T cell repertoire raised in response to NW8 was highly skewed and featured preferential use of a restricted set of V and J gene segments. Furthermore, as often seen in immunity against ancient viruses like CMV and Epstein-Barr virus (EBV), the response was strongly dominated by identical TCR sequences shared by multiple individuals, or "public" TCRs. Finally, we describe a pair "superdominant" TCR clonotypes, which were germline or nearly germline-encoded and produced at remarkably high frequencies in certain individuals, with a single CMV-specific clonotype representing up to 17% of all CD8+ T cells. Given the magnitude of the NW8 response, we propose that this major skewing of CMV-specific immunity leads to massive perturbations in the overall TCR repertoire in HLA-B * 44:03 individuals.

Published
2018
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42. Optimized Peptide-MHC Multimer Protocols for Detection and Isolation of Autoimmune T-Cells.

Author

Dolton G, Zervoudi E, Rius C, Wall A, Thomas HL, Fuller A, Yeo L, Legut M, Wheeler S, Attaf M, Chudakov DM, Choy E, Peakman M, and Sewell AK

Abstract

Peptide-MHC (pMHC) multimers have become the "gold standard" for the detection and isolation of antigen-specific T-cells but recent evidence shows that normal use of these reagents can miss fully functional T-cells that bear T-cell receptors (TCRs) with low affinity for cognate antigen. This issue is particularly pronounced for anticancer and autoimmune T-cells as self-reactive T-cell populations are enriched for low-affinity TCRs due to the removal of cells with higher affinity receptors by immune tolerance mechanisms. Here, we stained a wide variety of self-reactive human T-cells using regular pMHC staining and an optimized technique that included: (i) protein kinase inhibitor (PKI), to prevent TCR triggering and internalization, and (ii) anti-fluorochrome antibody, to reduce reagent dissociation during washing steps. Lymphocytes derived from the peripheral blood of type 1 diabetes patients were stained with pMHC multimers made with epitopes from preproinsulin (PPI), insulin-β chain, glutamic acid decarboxylase 65 (GAD65), or glucose-6-phospate catalytic subunit-related protein (IGRP) presented by disease-risk allelles HLA A*02:01 or HLA*24:02. Samples from ankylosing spondylitis patients were stained with a multimerized epitope from vasoactive intestinal polypeptide receptor 1 (VIPR1) presented by HLA B*27:05. Optimized procedures stained an average of 40.5-fold ( p  = 0.01, range between 1.4 and 198) more cells than could be detected without the inclusion of PKI and cross-linking anti-fluorochrome antibody. Higher order pMHC dextramers recovered more cells than pMHC tetramers in parallel assays, and standard staining protocols with pMHC tetramers routinely recovered less cells than functional assays. HLA A*02:01-restricted PPI-specific and HLA B*27:05-restricted VIPR1-specific T-cell clones generated using the optimized procedure could not be stained by standard pMHC tetramer staining. However, these clones responded well to exogenously supplied peptide and endogenously processed and presented epitopes. We also showed that anti-fluorochrome antibody-conjugated magnetic beads enhanced staining of self-reactive T-cells that could not be stained using standard protocols, thus enabling rapid ex vivo isolation of autoimmune T-cells. We, therefore, conclude that regular pMHC tetramer staining is generally unsuitable for recovering self-reactive T-cells from clinical samples and recommend the use of the optimized protocols described herein.

Published
2018
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43. VDJdb: a curated database of T-cell receptor sequences with known antigen specificity.

Author

Shugay M, Bagaev DV, Zvyagin IV, Vroomans RM, Crawford JC, Dolton G, Komech EA, Sycheva AL, Koneva AE, Egorov ES, Eliseev AV, Van Dyk E, Dash P, Attaf M, Rius C, Ladell K, McLaren JE, Matthews KK, Clemens EB, Douek DC, Luciani F, van Baarle D, Kedzierska K, Kesmir C, Thomas PG, Price DA, Sewell AK, and Chudakov DM

Subjects
Amino Acid Sequence, Animals, Antigens immunology, Antigens metabolism, Binding Sites, High-Throughput Nucleotide Sequencing, Humans, Internet, Macaca mulatta, Major Histocompatibility Complex genetics, Major Histocompatibility Complex immunology, Mice, Models, Molecular, Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Receptors, Antigen, T-Cell immunology, Receptors, Antigen, T-Cell metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Single-Cell Analysis, T-Lymphocytes cytology, T-Lymphocytes immunology, Antigens chemistry, Databases, Protein, Molecular Sequence Annotation, Receptors, Antigen, T-Cell chemistry, Software
Abstract

The ability to decode antigen specificities encapsulated in the sequences of rearranged T-cell receptor (TCR) genes is critical for our understanding of the adaptive immune system and promises significant advances in the field of translational medicine. Recent developments in high-throughput sequencing methods (immune repertoire sequencing technology, or RepSeq) and single-cell RNA sequencing technology have allowed us to obtain huge numbers of TCR sequences from donor samples and link them to T-cell phenotypes. However, our ability to annotate these TCR sequences still lags behind, owing to the enormous diversity of the TCR repertoire and the scarcity of available data on T-cell specificities. In this paper, we present VDJdb, a database that stores and aggregates the results of published T-cell specificity assays and provides a universal platform that couples antigen specificities with TCR sequences. We demonstrate that VDJdb is a versatile instrument for the annotation of TCR repertoire data, enabling a concatenated view of antigen-specific TCR sequence motifs. VDJdb can be accessed at https://vdjdb.cdr3.net and https://github.com/antigenomics/vdjdb-db., (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Published
2018
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44. PD-1 + Polyfunctional T Cells Dominate the Periphery after Tumor-Infiltrating Lymphocyte Therapy for Cancer.

Author

Donia M, Kjeldsen JW, Andersen R, Westergaard MCW, Bianchi V, Legut M, Attaf M, Szomolay B, Ott S, Dolton G, Lyngaa R, Hadrup SR, Sewell AK, and Svane IM

Subjects
Adult, Aged, Antigens, Neoplasm immunology, CD8-Positive T-Lymphocytes immunology, Female, Humans, Immunotherapy, Adoptive, Lymphocyte Activation immunology, Male, Melanoma genetics, Melanoma immunology, Melanoma pathology, Middle Aged, Programmed Cell Death 1 Ligand 2 Protein antagonists & inhibitors, Programmed Cell Death 1 Ligand 2 Protein immunology, Programmed Cell Death 1 Receptor antagonists & inhibitors, T-Lymphocytes, Cell- and Tissue-Based Therapy, Lymphocytes, Tumor-Infiltrating immunology, Melanoma therapy, Programmed Cell Death 1 Receptor immunology
Abstract

Purpose: Infusion of highly heterogeneous populations of autologous tumor-infiltrating lymphocytes (TIL) can result in tumor regression of exceptional duration. Initial tumor regression has been associated with persistence of tumor-specific TILs 1 month after infusion, but mechanisms leading to long-lived memory responses are currently unknown. Here, we studied the dynamics of bulk tumor-reactive CD8 + T-cell populations in patients with metastatic melanoma following treatment with TILs. Experimental Design: We analyzed the function and phenotype of tumor-reactive CD8 + T cells contained in serial blood samples of 16 patients treated with TILs. Results: Polyfunctional tumor-reactive CD8 + T cells accumulated over time in the peripheral lymphocyte pool. Combinatorial analysis of multiple surface markers (CD57, CD27, CD45RO, PD-1, and LAG-3) showed a unique differentiation pattern of polyfunctional tumor-reactive CD8 + T cells, with highly specific PD-1 upregulation early after infusion. The differentiation and functional status appeared largely stable for up to 1 year after infusion. Despite some degree of clonal diversification occurring in vivo within the bulk tumor-reactive CD8 + T cells, further analyses showed that CD8 + T cells specific for defined tumor antigens had similar differentiation status. Conclusions: We demonstrated that tumor-reactive CD8 + T-cell subsets that persist after TIL therapy are mostly polyfunctional, display a stable partially differentiated phenotype, and express high levels of PD-1. These partially differentiated PD-1 + polyfunctional TILs have a high capacity for persistence and may be susceptible to PD-L1/PD-L2-mediated inhibition. Clin Cancer Res; 23(19); 5779-88. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Published
2017
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45. αβ T cell receptors as predictors of health and disease.

Author

Attaf M, Huseby E, and Sewell AK

Subjects
Animals, Biomarkers, Humans, T-Lymphocytes pathology, Thymus Gland pathology, Antigens immunology, Histocompatibility Antigens immunology, Receptors, Antigen, T-Cell, alpha-beta immunology, T-Lymphocytes immunology, Thymus Gland immunology
Abstract

The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex (MHC) molecules at the cell surface. Interaction between peptide-MHC (pMHC) and the T cell receptor (TCR) is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR 'signatures' raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome.

Published
2015
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