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1. Mtb HLA-E-tetramer-sorted CD8+ T cells have a diverse TCR repertoire

Author

Voogd, Linda, Drittij, Anne M.H.F., Dingenouts, Calinda K.E., Franken, Kees L.M.C., Unen, Vincent van, van Meijgaarden, Krista E., Ruibal, Paula, Hagedoorn, Renate S., Leitner, Judith A., Steinberger, Peter, Heemskerk, Mirjam H.M., Davis, Mark M., Scriba, Thomas J., Ottenhoff, Tom H.M., and Joosten, Simone A.

Published
2024
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5. Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes

Author

Wawina-Bokalanga, Tony, Vanmechelen, Bert, Lhermitte, Valentine, Marti-Carreras, Joan, Vergote, Valentijn, Koundouno, Fara Raymond, Akoi-Bore, Joseph, Thom, Ruth, Tipton, Tom, Steeds, Kimberley, Moussa, Keita Balla, Amento, Ablam, Laenen, Lies, Duraffour, Sophie, Gabriel, Martin, Ruibal, Paula, Hall, Yper, Kader-Konde, Mandy, Gunther, Stephan, Baele, Guy, Munoz-Fontela, Cesar, Van Weyenbergh, Johan, Carroll, Miles W., and Maes, Piet

Subjects
Ebola virus infections -- Genetic aspects -- Development and progression -- Care and treatment, HLA histocompatibility antigens -- Health aspects, Immune response -- Genetic aspects, Killer cells -- Genetic aspects -- Health aspects, Cell receptors -- Health aspects, Histocompatibility antigens -- Health aspects, Health
Abstract

E bola virus (EBOV) is an enveloped, nonsegmented, negative-sense, single-stranded RNA virus that belongs to the genus Ebolavirus in the family Filoviridae. This genus comprises 6 species recognized by the [...]

Published
2021
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10. Thermal‐exchange HLA‐E multimers reveal specificity in HLA‐E and NKG2A / CD94 complex interactions

Author

Ruibal, Paula, primary, Derksen, Ian, additional, van Wolfswinkel, Marjolein, additional, Voogd, Linda, additional, Franken, Kees L. M. C., additional, El Hebieshy, Angela F., additional, van Hall, Thorbald, additional, Schoufour, Tom A. W., additional, Wijdeven, Ruud H., additional, Ottenhoff, Tom H. M., additional, Scheeren, Ferenc A., additional, and Joosten, Simone A., additional

Published
2022
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11. Identification of HLA-E Binding Mycobacterium tuberculosis–Derived Epitopes through Improved Prediction Models

Author

Ruibal, Paula, primary, Franken, Kees L. M. C., additional, van Meijgaarden, Krista E., additional, van Wolfswinkel, Marjolein, additional, Derksen, Ian, additional, Scheeren, Ferenc A., additional, Janssen, George M. C., additional, van Veelen, Peter A., additional, Sarfas, Charlotte, additional, White, Andrew D., additional, Sharpe, Sally A., additional, Palmieri, Fabrizio, additional, Petrone, Linda, additional, Goletti, Delia, additional, Abeel, Thomas, additional, Ottenhoff, Tom H. M., additional, and Joosten, Simone A., additional

Published
2022
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12. Avatar Mice Underscore the Role of the T Cell-Dendritic Cell Crosstalk in Ebola Virus Disease and Reveal Mechanisms of Protection in Survivors

Author

Rottstegge, Monika, primary, Tipton, Tom, additional, Oestereich, Lisa, additional, Ruibal, Paula, additional, Nelson, Emily V., additional, Olal, Catherine, additional, Port, Julia R., additional, Seibel, Johan, additional, Pallasch, Elisa, additional, Bockholt, Sabrina, additional, Koundouno, Fara Raymond, additional, Boré, Joseph Akoi, additional, Rodríguez, Estefanía, additional, Escudero-Pérez, Beatriz, additional, Günther, Stephan, additional, Carroll, Miles W., additional, and Muñoz-Fontela, César, additional

Published
2022
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13. Unique human immune signature of Ebola virus disease in Guinea

Author

Ruibal, Paula, Oestereich, Lisa, Ldtke, Anja, Becker-Ziaja, Beate, Wozniak, David M., Kerber, Romy, Korva, Mia, Cabeza-Cabrerizo, Mar, Bore, Joseph A., Koundouno, Fara Raymond, Duraffour, Sophie, Weller, Romy, Thorenz, Anja, Cimini, Eleonora, Viola, Domenico, Agrati, Chiara, Repits, Johanna, Afrough, Babak, Cowley, Lauren A., Ngabo, Didier, Hinzmann, Julia, Mertens, Marc, Vitoriano, Ins, Logue, Christopher H., Boettcher, Jan Peter, Pallasch, Elisa, Sachse, Andreas, Bah, Amadou, Nitzsche, Katja, Kuisma, Eeva, Michel, Janine, Holm, Tobias, Zekeng, Elsa-Gayle, Garca-Dorival, Isabel, Wlfel, Roman, Stoecker, Kilian, Fleischmann, Erna, Strecker, Thomas, Di Caro, Antonino, Avi-upanc, Tatjana, Kurth, Andreas, Meschi, Silvia, Mly, Stephane, Newman, Edmund, Bocquin, Anne, Kis, Zoltan, Kelterbaum, Anne, Molkenthin, Peter, Carletti, Fabrizio, Portmann, Jasmine, Wolff, Svenja, Castilletti, Concetta, Schudt, Gordian, Fizet, Alexandra, Ottowell, Lisa J., Herker, Eva, Jacobs, Thomas, Kretschmer, Birte, Severi, Ettore, Ouedraogo, Nobila, Lago, Mar, Negredo, Anabel, Franco, Leticia, Anda, Pedro, Schmiedel, Stefan, Kreuels, Benno, Wichmann, Dominic, Addo, Marylyn M., Lohse, Ansgar W., De Clerck, Hilde, Nanclares, Carolina, Jonckheere, Sylvie, Van Herp, Michel, Sprecher, Armand, Xiaojiang, Gao, Carrington, Mary, Miranda, Osvaldo, Castro, Carlos M., Gabriel, Martin, Drury, Patrick, Formenty, Pierre, Diallo, Boubacar, Koivogui, Lamine, Magassouba, NFaly, Carroll, Miles W., Gnther, Stephan, and Muoz-Fontela, Csar

Subjects
Ebola hemorrhagic fever -- Physiological aspects, Medical research, Immune response -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Paula Ruibal [1, 2, 3, 4]; Lisa Oestereich [2, 3, 4]; Anja Ldtke [1, 2, 3, 4]; Beate Becker-Ziaja [2, 3, 4]; David M. Wozniak [2, 3, 4]; Romy [...]

Published
2016
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14. Identification of HLA-E Binding Mycobacterium tuberculosis-Derived Epitopes through Improved Prediction Models

Author

Ruibal, Paula (author), Franken, Kees L.M.C. (author), van Meijgaarden, Krista E. (author), van Wolfswinkel, Marjolein (author), Derksen, Ian (author), Scheeren, Ferenc A. (author), van Veelen, Peter A. (author), Abeel, T.E.P.M.F. (author), Joosten, Simone A. (author), Ruibal, Paula (author), Franken, Kees L.M.C. (author), van Meijgaarden, Krista E. (author), van Wolfswinkel, Marjolein (author), Derksen, Ian (author), Scheeren, Ferenc A. (author), van Veelen, Peter A. (author), Abeel, T.E.P.M.F. (author), and Joosten, Simone A. (author)

Abstract

Tuberculosis (TB) remains one of the deadliest infectious diseases worldwide, posing great social and economic burden to affected countries. Novel vaccine approaches are needed to increase protective immunity against the causative agent Mycobacterium tuberculosis (Mtb) and to reduce the development of active TB disease in latently infected individuals. Donor-unrestricted T cell responses represent such novel potential vaccine targets. HLA-E-restricted T cell responses have been shown to play an important role in protection against TB and other infections, and recent studies have demonstrated that these cells can be primed in vitro. However, the identification of novel pathogen-derived HLA-E binding peptides presented by infected target cells has been limited by the lack of accurate prediction algorithms for HLA-E binding. In this study, we developed an improved HLA-E binding peptide prediction algorithm and implemented it to identify (to our knowledge) novel Mtb-derived peptides with capacity to induce CD8+ T cell activation and that were recognized by specific HLA-E-restricted T cells in Mycobacterium-exposed humans. Altogether, we present a novel algorithm for the identification of pathogen- or self-derived HLA-E-presented peptides., Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Pattern Recognition and Bioinformatics

Published
2022
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15. Thermal‐exchange HLA‐E multimers reveal specificity in HLA‐E and NKG2A/CD94 complex interactions.

Author

Ruibal, Paula, Derksen, Ian, van Wolfswinkel, Marjolein, Voogd, Linda, Franken, Kees L. M. C., El Hebieshy, Angela F., van Hall, Thorbald, Schoufour, Tom A. W., Wijdeven, Ruud H., Ottenhoff, Tom H. M., Scheeren, Ferenc A., and Joosten, Simone A.

Subjects
*PEPTIDES, *ANTIGEN presentation, *T cells, *FLOW cytometry, *COMMUNICABLE diseases
Abstract

There is growing interest in HLA‐E‐restricted T‐cell responses as a possible novel, highly conserved, vaccination targets in the context of infectious and malignant diseases. The developing field of HLA multimers for the detection and study of peptide‐specific T cells has allowed the in‐depth study of TCR repertoires and molecular requirements for efficient antigen presentation and T‐cell activation. In this study, we developed a method for efficient peptide thermal exchange on HLA‐E monomers and multimers allowing the high‐throughput production of HLA‐E multimers. We optimized the thermal‐mediated peptide exchange, and flow cytometry staining conditions for the detection of TCR and NKG2A/CD94 receptors, showing that this novel approach can be used for high‐throughput identification and analysis of HLA‐E‐binding peptides which could be involved in T‐cell and NK cell‐mediated immune responses. Importantly, our analysis of NKG2A/CD94 interaction in the presence of modified peptides led to new molecular insights governing the interaction of HLA‐E with this receptor. In particular, our results reveal that interactions of HLA‐E with NKG2A/CD94 and the TCR involve different residues. Altogether, we present a novel HLA‐E multimer technology based on thermal‐mediated peptide exchange allowing us to investigate the molecular requirements for HLA‐E/peptide interaction with its receptors. [ABSTRACT FROM AUTHOR]

Published
2023
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18. Ebola Virus Disease Survivors Show More Efficient Antibody Immunity than Vaccinees Despite Similar Levels of Circulating Immunoglobulins

Author

Koch, Till, primary, Rottstegge, Monika, additional, Ruibal, Paula, additional, Gomez-Medina, Sergio, additional, Nelson, Emily V., additional, Escudero-Pérez, Beatriz, additional, Pillny, Matthias, additional, Ly, My Linh, additional, Koundouno, Fara Raymond, additional, Bore, Joseph Akoi, additional, Magassouba, N’Faly, additional, Dahlke, Christine, additional, Günther, Stephan, additional, Carroll, Miles W., additional, Addo, Marylyn M., additional, and Muñoz-Fontela, César, additional

Published
2020
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19. Monocyte‐derived dendritic cells enhance protection against secondary influenza challenge by controlling the switch in CD8+ T‐cell immunodominance

Author

Cruz, Jazmina L. G., Pérez‐Girón, José V., Lüdtke, Anja, Gómez‐Medina, Sergio, Ruibal, Paula, Idoyaga, Juliana, and Muñoz‐Fontela, César

Subjects
Mice, Knockout, Mice, Inbred BALB C, CD8+ T cell · Dendritic cell · Immunodominance · Influenza virus · Monocyte, Immunodominant Epitopes, Short Communication, Viral Core Proteins, Immunity to infection, Mice, Transgenic, T-Cell Antigen Receptor Specificity, Dendritic Cells, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Monocytes, Short Communication|Basic, Mice, Inbred C57BL, Mice, Influenza A Virus, H1N1 Subtype, Orthomyxoviridae Infections, Animals, Basic, Immunologic Memory, Lung, Cells, Cultured
Abstract

Influenza virus infection triggers an increase in the number of monocyte‐derived dendritic cells (moDCs) in the respiratory tract, but the role of these cells during antiviral immunity is still unclear. Here we show that during influenza infection, moDCs dominate the late activation of CD8+ T cells and trigger the switch in immunodominance of the CD8+ T‐cell response from acidic polymerase specificity to nucleoprotein specificity. Abrogation of monocyte recruitment or depletion of moDCs strongly compromised host resistance to secondary influenza challenge. These findings underscore a novel function of moDCs in the antiviral response to influenza virus, and have important implications for vaccine design.

Published
2016

20. Comparative pathogenesis of Ebola virus and Reston virus infection in humanized mice

Author

Escudero-Pérez, Beatriz, primary, Ruibal, Paula, additional, Rottstegge, Monika, additional, Lüdtke, Anja, additional, Port, Julia R., additional, Hartmann, Kristin, additional, Gómez-Medina, Sergio, additional, Müller-Guhl, Jürgen, additional, Nelson, Emily V., additional, Krasemann, Susanne, additional, Rodríguez, Estefanía, additional, and Muñoz-Fontela, César, additional

Published
2019
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21. Beziehung zwischen HLA und T-Zell-Reaktionen auf Ebola-Virus

Author

Ruibal, Paula, Dotzauer, Andreas, and Munoz-Fontela, César

Subjects
HLA, Ebola virus, ddc:570, T cells, 570 Life sciences, biology
Abstract

Ebola virus disease (EVD) is a severe illness caused by infection with Ebola virus (EBOV) which causes sporadic outbreaks in African countries, the last one taking place in West Africa and affecting over 28000 people. Even though several decades have passed since the description of the first EVD cases, there are still many unanswered questions regarding the involvement of the human immune response in the pathophysiology of EVD. Research in this field is challenging because of the requirement of biosafety level 4 containment and the scarcity of human data. During the last EVD outbreak in West Africa, we had the opportunity to establish an immunology lab at Donka hospital in Conakry, Guinea where we collected and analysed leftover blood samples from patients diagnosed by the European Mobile Laboratory. With the use of benchtop multiparametric flow cytometry and subsequent analysis in the biosafety level 4 laboratory in Hamburg, we evaluated the kinetics and phenotype of antigen-presenting cells as well as T cells with the goal to identify immune biomarkers of disease outcome. Our approach was to utilize flow cytometry to characterize cell profiles in blood as well as immunogenetics, in particular analysis of the T-cell receptor clonotypes and HLA polymorphisms. Immune data was then correlated with clinical and epidemiological findings to try to detect potential predictors of outcome and targets for immunotherapy. Our observations highlight the importance of CD16 monocytes in the innate immune response to EBOV infection and in viral clearance. Additionally, we could identify a dysregulation of the adaptive immune response in fatal cases, characterised by the upregulation of the T cell inhibitory markers CTLA-4 and PD-1 and the inability to control viral replication. These results identify CD16 monocytes and the regulatory pathways of T cell responses as potential targets for post-exposure EVD immunotherapy. Moreover, our immunogenetics study evidenced the relevance of the expression of various HLA alleles and the activation of a T cell response through a broad and diverse T cell receptor repertoire in improved disease outcome.

Published
2017

24. Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections

Author

Cimini, Eleonora, primary, Viola, Domenico, additional, Cabeza-Cabrerizo, Mar, additional, Romanelli, Antonella, additional, Tumino, Nicola, additional, Sacchi, Alessandra, additional, Bordoni, Veronica, additional, Casetti, Rita, additional, Turchi, Federica, additional, Martini, Federico, additional, Bore, Joseph A., additional, Koundouno, Fara Raymond, additional, Duraffour, Sophie, additional, Michel, Janine, additional, Holm, Tobias, additional, Zekeng, Elsa Gayle, additional, Cowley, Lauren, additional, Garcia Dorival, Isabel, additional, Doerrbecker, Juliane, additional, Hetzelt, Nicole, additional, Baum, Jonathan H. J., additional, Portmann, Jasmine, additional, Wölfel, Roman, additional, Gabriel, Martin, additional, Miranda, Osvaldo, additional, Díaz, Graciliano, additional, Díaz, José E., additional, Fleites, Yoel A., additional, Piñeiro, Carlos A., additional, Castro, Carlos M., additional, Koivogui, Lamine, additional, Magassouba, N’Faly, additional, Diallo, Boubacar, additional, Ruibal, Paula, additional, Oestereich, Lisa, additional, Wozniak, David M., additional, Lüdtke, Anja, additional, Becker-Ziaja, Beate, additional, Capobianchi, Maria R., additional, Ippolito, Giuseppe, additional, Carroll, Miles W., additional, Günther, Stephan, additional, Di Caro, Antonino, additional, Muñoz-Fontela, César, additional, and Agrati, Chiara, additional

Published
2017
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25. Ebola virus infection kinetics in chimeric mice reveal a key role of T cells as barriers for virus dissemination

Author

Lüdtke, Anja, primary, Ruibal, Paula, additional, Wozniak, David M., additional, Pallasch, Elisa, additional, Wurr, Stephanie, additional, Bockholt, Sabrina, additional, Gómez-Medina, Sergio, additional, Qiu, Xiangguo, additional, Kobinger, Gary P., additional, Rodríguez, Estefanía, additional, Günther, Stephan, additional, Krasemann, Susanne, additional, Idoyaga, Juliana, additional, Oestereich, Lisa, additional, and Muñoz-Fontela, César, additional

Published
2017
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26. Regulation of Ebola virus VP40 matrix protein by SUMO

Author

Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Baz-Martínez, Maite, El Motiam, Ahmed, Ruibal, Paula, Condezo Castro, Gabriela Nérida, de la Cruz Herrera, Carlos F., Lang, Valerie, Collado, Manuel, San Martín, Carmen, Rodríguez, Manuel S., Muñoz Fontela, Cesar, Rivas, Carmen, Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Baz-Martínez, Maite, El Motiam, Ahmed, Ruibal, Paula, Condezo Castro, Gabriela Nérida, de la Cruz Herrera, Carlos F., Lang, Valerie, Collado, Manuel, San Martín, Carmen, Rodríguez, Manuel S., Muñoz Fontela, Cesar, and Rivas, Carmen

Abstract

The matrix protein of Ebola virus (EBOV) VP40 regulates viral budding, nucleocapsid recruitment, virus structure and stability, viral genome replication and transcription, and has an intrinsic ability to form virus-like particles. The elucidation of the regulation of VP40 functions is essential to identify mechanisms to inhibit viral replication and spread. Post-translational modifications of proteins with ubiquitin-like family members are common mechanisms for the regulation of host and virus multifunctional proteins. Thus far, no SUMOylation of VP40 has been described. Here we demonstrate that VP40 is modified by SUMO and that SUMO is included into the viral like particles (VLPs). We demonstrate that lysine residue 326 in VP40 is involved in SUMOylation, and by analyzing a mutant in this residue we show that SUMO conjugation regulates the stability of VP40 and the incorporation of SUMO into the VLPs. Our study indicates for the first time, to the best of our knowledge, that EBOV hijacks the cellular SUMOylation system in order to modify its own proteins. Modulation of the VP40-SUMO interaction may represent a novel target for the therapy of Ebola virus infection

Published
2016

27. Regulation of Ebola virus VP40 matrix protein by SUMO

Author

Baz-Martínez, Maite, primary, El Motiam, Ahmed, additional, Ruibal, Paula, additional, Condezo, Gabriela N., additional, de la Cruz-Herrera, Carlos F., additional, Lang, Valerie, additional, Collado, Manuel, additional, San Martín, Carmen, additional, Rodríguez, Manuel S., additional, Muñoz-Fontela, Cesar, additional, and Rivas, Carmen, additional

Published
2016
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28. Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16 + Monocytes

Author

Lüdtke, Anja, primary, Ruibal, Paula, additional, Becker-Ziaja, Beate, additional, Rottstegge, Monika, additional, Wozniak, David M., additional, Cabeza-Cabrerizo, Mar, additional, Thorenz, Anja, additional, Weller, Romy, additional, Kerber, Romy, additional, Idoyaga, Juliana, additional, Magassouba, N'Faly, additional, Gabriel, Martin, additional, Günther, Stephan, additional, Oestereich, Lisa, additional, and Muñoz-Fontela, César, additional

Published
2016
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29. Chimeric Mice with Competent Hematopoietic Immunity Reproduce Key Features of Severe Lassa Fever

Author

Oestereich, Lisa, primary, Lüdtke, Anja, additional, Ruibal, Paula, additional, Pallasch, Elisa, additional, Kerber, Romy, additional, Rieger, Toni, additional, Wurr, Stephanie, additional, Bockholt, Sabrina, additional, Pérez-Girón, José V., additional, Krasemann, Susanne, additional, Günther, Stephan, additional, and Muñoz-Fontela, César, additional

Published
2016
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31. Ebola Virus Disease in Mice with Transplanted Human Hematopoietic Stem Cells

Author

Lüdtke, Anja, primary, Oestereich, Lisa, additional, Ruibal, Paula, additional, Wurr, Stephanie, additional, Pallasch, Elisa, additional, Bockholt, Sabrina, additional, Ip, Wing Hang, additional, Rieger, Toni, additional, Gómez-Medina, Sergio, additional, Stocking, Carol, additional, Rodríguez, Estefanía, additional, Günther, Stephan, additional, and Muñoz-Fontela, César, additional

Published
2015
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32. Monocyte-derived dendritic cells enhance protection against secondary influenza challenge by controlling the switch in CD8+ T-cell immunodominance.

Author

Cruz, Jazmina L. G., Pérez‐Girón, José V., Lüdtke, Anja, Gómez‐Medina, Sergio, Ruibal, Paula, Idoyaga, Juliana, and Muñoz‐Fontela, César

Abstract

Influenza virus infection triggers an increase in the number of monocyte-derived dendritic cells (moDCs) in the respiratory tract, but the role of these cells during antiviral immunity is still unclear. Here we show that during influenza infection, moDCs dominate the late activation of CD8+ T cells and trigger the switch in immunodominance of the CD8+ T-cell response from acidic polymerase specificity to nucleoprotein specificity. Abrogation of monocyte recruitment or depletion of moDCs strongly compromised host resistance to secondary influenza challenge. These findings underscore a novel function of moDCs in the antiviral response to influenza virus, and have important implications for vaccine design. [ABSTRACT FROM AUTHOR]

Published
2017
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33. Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16+ Monocytes.

Author

Lüdtke, Anja, Ruibal, Paula, Becker-Ziaja, Beate, Rottstegge, Monika, Wozniak, David M., Cabeza-Cabrerizo, Mar, Thorenz, Anja, Weller, Romy, Kerber, Romy, Idoyaga, Juliana, Magassouba, N'Faly, Gabriel, Martin, Günther, Stephan, Oestereich, Lisa, and Muñoz-Fontela, César

Subjects
*EBOLA virus disease, *CD antigens, *VIRUS inactivation, *MONOCYTES, *DENDRITIC cells, *NEUTROPHILS, *DIAGNOSIS
Abstract

A number of previous studies have identified antigen-presenting cells (APCs) as key targets of Ebola virus (EBOV), but the role of APCs in human Ebola virus disease (EVD) is not known. We have evaluated the phenotype and kinetics of monocytes, neutrophils, and dendritic cells (DCs) in peripheral blood of patients for whom EVD was diagnosed by the European Mobile Laboratory in Guinea. Acute EVD was characterized by reduced levels of circulating nonclassical CD16+ monocytes with a poor activation profile. In survivors, CD16+ monocytes were activated during recovery, coincident with viral clearance, suggesting an important role of this cell subset in EVD pathophysiology. [ABSTRACT FROM AUTHOR]

Published
2016
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34. Longitudinal soluble marker profiles reveal strong association between cytokine storms resulting from macrophage activation and disease severity in COVID-19 disease.

Author

van Meijgaarden KE, van Veen S, Tsonaka R, Ruibal P, Roukens AHE, Arbous SM, Manniën J, Cannegieter SC, Ottenhoff THM, and Joosten SA

Subjects
Humans, Male, Female, Middle Aged, SARS-CoV-2 isolation & purification, Cytokines blood, Cytokine Release Syndrome blood, Adult, Aged, Serum Amyloid P-Component metabolism, Serum Amyloid P-Component analysis, C-Reactive Protein, COVID-19 blood, COVID-19 immunology, Biomarkers blood, Severity of Illness Index, Macrophage Activation
Abstract

SARS-CoV2 infection results in a range of disease severities, but the underlying differential pathogenesis is still not completely understood. At presentation it remains difficult to estimate and predict severity, in particular, identify individuals at greatest risk of progression towards the most severe disease-states. Here we used advanced models with circulating serum analytes as variables in combination with daily assessment of disease severity using the SCODA-score, not only at single time points but also during the course of disease, to correlate analyte levels and disease severity. We identified a remarkably strong pro-inflammatory cytokine/chemokine profile with high levels for sCD163, CCL20, HGF, CHintinase3like1 and Pentraxin3 in serum which correlated with COVID-19 disease severity and overall outcome. Although precise analyte levels differed, resulting biomarker profiles were highly similar at early and late disease stages, and even during convalescence similar biomarkers were elevated and further included CXCL3, CXCL6 and Osteopontin. Taken together, strong pro-inflammatory marker profiles were identified in patients with COVID-19 disease which correlated with overall outcome and disease severity., (© 2024. The Author(s).)

Published
2024
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35. Discovery of HLA-E-Presented Epitopes: MHC-E/Peptide Binding and T-Cell Recognition.

Author

Ruibal P, Franken KLMC, van Meijgaarden KE, Walters LC, McMichael AJ, Gillespie GM, Joosten SA, and Ottenhoff THM

Subjects
Epitopes, Humans, Peptides, HLA-E Antigens, Histocompatibility Antigens Class I metabolism, T-Lymphocytes
Abstract

Understanding the interactions involved during the immunological synapse between peptide, HLA-E molecules, and TCR is crucial to effectively target protective HLA-E-restricted T-cell responses in humans. Here we describe three techniques based on the generation of MHC-E/peptide complexes (MHC-E generically includes HLA-E-like molecules in human and nonhuman species, while HLA-E specifically refers to human molecules), which allow to investigate MHC-E/peptide binding at the molecular level through binding assays and by using peptide loaded HLA-E tetramers, to detect, isolate, and study peptide-specific HLA-E-restricted human T-cells., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2022
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36. Monocyte-derived dendritic cells enhance protection against secondary influenza challenge by controlling the switch in CD8 + T-cell immunodominance.

Author

Cruz JL, Pérez-Girón JV, Lüdtke A, Gómez-Medina S, Ruibal P, Idoyaga J, and Muñoz-Fontela C

Subjects
Animals, Cells, Cultured, Dendritic Cells virology, Immunodominant Epitopes immunology, Immunologic Memory, Lung virology, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Viral Core Proteins immunology, CD8-Positive T-Lymphocytes immunology, Dendritic Cells immunology, Influenza A Virus, H1N1 Subtype immunology, Lung immunology, Monocytes immunology, Orthomyxoviridae Infections immunology, T-Cell Antigen Receptor Specificity
Abstract

Influenza virus infection triggers an increase in the number of monocyte-derived dendritic cells (moDCs) in the respiratory tract, but the role of these cells during antiviral immunity is still unclear. Here we show that during influenza infection, moDCs dominate the late activation of CD8 + T cells and trigger the switch in immunodominance of the CD8 + T-cell response from acidic polymerase specificity to nucleoprotein specificity. Abrogation of monocyte recruitment or depletion of moDCs strongly compromised host resistance to secondary influenza challenge. These findings underscore a novel function of moDCs in the antiviral response to influenza virus, and have important implications for vaccine design., (© 2016 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2017
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