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1. Acute GVHD, BK virus hemorrhagic cystitis and age are risk factors for transplant-associated thrombotic microangiopathy in adults

Author

Vasu, Sumithira, Bostic, Matthew, Zhao, Qiuhong, Sharma, Nidhi, Puto, Marcin, Knight, Samantha, Scott, Denise, Guzman, Rosalyn, Kromer, Meghan, Tackett, Karen, Lind, Kristin, Knill, Kathryn, Watson, Emily, Wall, Sarah, Saad, Ayman, Choe, Hannah, Larkin, Karilyn, Brammer, Jonathan, Jaglowski, Samantha, Penza, Sam, Davies, Stella M., and Cataland, Spero

Published
2022
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3. Peptide Repertoire Changes Caused by Defects in Antigen Processing

Author

Lind, Kristin

Subjects
Immunology
Abstract

Peptide Repertoire Changes Caused by Defects in Antigen ProcessingByKristin Camfield LindDoctor of Philosophy in Molecular and Cell BiologyUniversity of California, BerkeleyProfessor Nilabh Shastri, ChairMHC I molecules display peptides derived from intracellular proteins on the cell surface for recognition by CD8+ T cells. Presentation of these peptide:MHC I complexes (pMHC I) is important for elimination of viruses and transformed cells. In order to generate an effective CD8 T cell response, a high-quality set of pMHC I must be presented. However, the editing mechanisms that select these optimal pMHC I are not clear. In these studies, we used biochemical and immunological methods to examine the role of two ER-resident pMHC I editors, tapasin and ERAAP in shaping the pMHC I repertoire. Analysis of tapasin-deficient mice revealed a qualitative loss as well as gain of some pMHC I. However, these changes did not overlap with the ERAAP-unedited pMHC I repertoire, indicating that tapasin edits peptides in a distinct way. Sequencing of peptides unique to tapasin-deficient cells revealed altered C-termini, suggesting that tapasin determines the peptide C-terminus while ERAAP shapes the peptide N-terminus. We separately examined the allele-specific effects of ERAAP-deficiency on the H-2d pMHC I repertoire. In addition to Kd and Dd, these mice express Ld, an MHC I molecule which is particularly affected by loss of ERAAP. We found that ERAAP-deficiency has distinct effects on the peptide repertoire presented by each MHC I molecule. Analysis of the peptide sequences revealed unique peptides bound to all three MHC I, although long, structurally unique peptides were only found on Dd and Kd. Furthermore, using a T cell hybridoma specific for loss of ERAAP function, we identified and characterized an ERAAP-unedited peptide presented by Dd. Together, these findings highlight the importance of both tapasin and ERAAP in determining an optimal pMHC I repertoire.

Published
2013

4. Abstract LB-306: Impacting Humoral Hypercalcemia of Malignancy (HHM) and associated PTH1R-mediated morbidities: Characterization of an anti-PTH1R antagonist monoclonal antibody to reverse hypercalcemia

Author

Mirza, Amer M., primary, Choppin, Agnes, additional, Bedinger, Daniel, additional, Hunt, Rachel, additional, Cotter, Robyn, additional, Pongo, Elizabeth, additional, Ahluwalia, Kiran, additional, Tran, Catarina, additional, Lao, Llewelyn, additional, Lind, Kristin, additional, Wijesuriya, Sujeewa, additional, Webster, Lynn, additional, Zhang, Fangjiu, additional, Johnson, Kirk, additional, Takeuchi, Toshihiko, additional, and Levy, Raphael, additional

Published
2017
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5. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): late breaking abstracts

Author

Althammer, Sonja, primary, Steele, Keith, additional, Rebelatto, Marlon, additional, Tan, Tze Heng, additional, Wiestler, Tobias, additional, Schmidt, Guenter, additional, Higgs, Brandon, additional, Li, Xia, additional, Shi, Li, additional, Jin, Xiaoping, additional, Antal, Joyce, additional, Gupta, Ashok, additional, Ranade, Koustubh, additional, Binning, Gerd, additional, Bellmunt, Joaquim, additional, de Wit, Ronald, additional, Vaughn, David J., additional, Fradet, Yves, additional, Lee, Jae Lyun, additional, Fong, Lawrence, additional, Vogelzang, Nicholas J., additional, Climent, Miguel A., additional, Petrylak, Daniel P., additional, Choueiri, Toni K., additional, Necchi, Andrea, additional, Gerritsen, Winald, additional, Gurney, Howard, additional, Quinn, David I., additional, Culine, Stéphane, additional, Sternberg, Cora N., additional, Mai, Yabing, additional, Puhlmann, Markus, additional, Perini, Rodolfo F., additional, Bajorin, Dean F., additional, Sharma, Padmanee, additional, Callahan, Margaret K., additional, Calvo, Emiliano, additional, Kim, Joseph W., additional, de Braud, Filipo, additional, Ott, Patrick A., additional, Bono, Petri, additional, Pillai, Rathi N., additional, Morse, Michael, additional, Le, Dung T., additional, Taylor, Matthew, additional, Spilliopoulou, Pavlina, additional, Bendell, Johanna, additional, Jaeger, Dirk, additional, Chan, Emily, additional, Antonia, Scott J., additional, Ascierto, Paolo A., additional, Hennicken, Delphine, additional, Tschaika, Marina, additional, Azrilevich, Alex, additional, Rosenberg, Jonathan, additional, Levy, Ofer, additional, Chan, Christopher, additional, Cojocaru, Gady, additional, Liang, Spencer, additional, Ophir, Eran, additional, Ganguly, Sudipto, additional, Toporik, Amir, additional, Kotturi, Maya, additional, Kfir, Tal Fridman, additional, Murter, Benjamin M., additional, Logronio, Kathryn, additional, Dassa, Liat, additional, Leung, Ling, additional, Greenwald, Shirley, additional, Azulay, Meir, additional, Kumar, Sandeep, additional, Alteber, Zoya, additional, Pan, Xiaoyu, additional, Machlenkin, Arthur, additional, Benita, Yair, additional, Drake, Andrew W., additional, Chajut, Ayelet, additional, Salomon, Ran, additional, Vankin, Ilan, additional, Safyon, Einav, additional, Hunter, John, additional, Levine, Zurit, additional, White, Mark, additional, Leidner, Rom, additional, Kang, Hyunseok, additional, Haddad, Robert, additional, Segal, Neil H., additional, Wirth, Lori J., additional, Ferris, Robert L., additional, Hodi, F. Stephen, additional, Sanborn, Rachel E., additional, Gajewski, Thomas F., additional, Sharfman, William, additional, McDonald, Dan, additional, Srivastava, Shivani, additional, Gu, Xuemin, additional, Phillips, Penny, additional, Passey, Chaitali, additional, Seiwert, Tanguy, additional, Habtetsion, Tsadik, additional, Zhou, Gang, additional, Sakellariou-Thompson, Donastas, additional, Haymaker, Cara, additional, Creasy, Caitlin, additional, Hurd, Mark, additional, Uraoka, Naohiro, additional, Canales, Jaime Rodriguez, additional, Koptez, Scott, additional, Hwu, Patrick, additional, Maitra, Anirban, additional, Bernatchez, Chantale, additional, Coyle, Scott M., additional, Roybel, Kole T., additional, Rupp, Levi J., additional, Santoro, Stephen P., additional, Secrest, Stephanie, additional, Spelman, Michael, additional, Ho, Hanson, additional, Gomes, Tina, additional, Tse, Tiffany, additional, Yung-Wu, Chia, additional, Taunton, Jack, additional, Lim, Wendell, additional, Emtage, Peter, additional, Moudgil, Tarsem, additional, Ballesteros-Merino, Carmen, additional, Hilton, Traci, additional, Paustian, Christopher, additional, Page, David, additional, Urba, Walter, additional, Fox, Bernard, additional, Bell, Bryan, additional, Patel, Ashish, additional, Olafsen, Tove, additional, Satpayev, Daulet, additional, Torgov, Michael, additional, Marchioni, Filippo, additional, Romero, Jason, additional, Jiang, Ziyue Karen, additional, Zamilpa, Charles, additional, Keppler, Jennifer S., additional, Mascioni, Alessandro, additional, Jia, Fang, additional, Lee, Chen-Yu, additional, Gudas, Jean, additional, Sullivan, Ryan J., additional, Hoshida, Yujin, additional, Logan, Theodore, additional, Khushalani, Nikhil, additional, Giobbie-Hurder, Anita, additional, Margolin, Kim, additional, Roder, Joanna, additional, Bhatt, Rupal, additional, Koon, Henry, additional, Olencki, Thomas, additional, Hutson, Thomas, additional, Curti, Brendan, additional, Blackmon, Shauna, additional, Mier, James W., additional, Puzanov, Igor, additional, Roder, Heinrich, additional, Stewart, John, additional, Amin, Asim, additional, Ernstoff, Marc S., additional, Clark, Joseph I., additional, Atkins, Michael B., additional, Kaufman, Howard L., additional, Sosman, Jeffrey, additional, Signoretti, Sabina, additional, McDermott, David F., additional, Anderson, Abraham A., additional, Milhem, Mohammed M., additional, Andtbacka, Robert H. I., additional, Minor, David, additional, Gorski, Kevin S., additional, Baker, Daniel M., additional, Hamid, Omid, additional, Akporiaye, Emmanuel, additional, Koguchi, Yoshinobu, additional, Sutcliffe, Kim, additional, Conder, Kristie, additional, Marron, Thomas, additional, Bhardwaj, Nina, additional, Hammerich, Linda, additional, George, Fiby, additional, Kim-Schulze, Seunghee, additional, Keler, Tibor, additional, Davis, Tom, additional, Crowley, Elizabeth, additional, Salazar, Andres, additional, Brody, Joshua, additional, Monjazeb, Arta, additional, Daly, Megan E., additional, Riess, Jonathan, additional, Li, Tianhong, additional, Murphy, William J., additional, Kelly, Karen, additional, Hu, Zhiwei, additional, Shen, Rulong, additional, Campbell, Amanda, additional, McMichael, Elizabeth, additional, Yu, Lianbo, additional, Ramaswam, Bhuvaneswari, additional, London, Cheryl A., additional, Xu, Tian, additional, Carson, William, additional, Kokolus, Kathleen M., additional, Repasky, Elizabeth A., additional, Schell, Todd D., additional, Drabick, Joseph D., additional, Messenheimer, David J., additional, Jensen, Shawn, additional, Rubinstein, Mark, additional, Andrijauskaite, Kristina, additional, Swiderska-syn, Marzena, additional, Lind, Kristin, additional, Choppin, Agnes, additional, Roell, Marina K., additional, Wrangle, John, additional, Rhode, Peter, additional, Wong, Hing, additional, Ahmad, Shamim, additional, Webb, Mason, additional, Abu-Eid, Rasha, additional, Shrimali, Rajeev, additional, Verma, Vivek, additional, Doroodchi, Atbin, additional, Berrong, Zuzana, additional, Yashar, David, additional, Samara, Raed, additional, Mkrtichyan, Mikayel, additional, Khleif, Samir, additional, Powell, Steven, additional, Gitau, Mark, additional, Sumey, Christopher, additional, Terrell, Andrew, additional, Lohr, Michele, additional, Nowak, Ryan K., additional, McGraw, Steven, additional, Jensen, Ash, additional, Blanchard, Miran, additional, Gold, Kathryn A., additional, Cohen, Ezra E. W., additional, Ellison, Christie, additional, Black, Lora, additional, Lee, John, additional, Spanos, William Chad, additional, Wennerberg, Erik, additional, Schwitzer, Emily, additional, Lhuillier, Claire, additional, Koelwyn, Graeme, additional, Hiner, Rebecca, additional, Jones, Lee, additional, Demaria, Sandra, additional, Amanda, Vandeveer, additional, Greiner, John W., additional, Schlom, Jeffrey, additional, Bookstaver, Michelle, additional, Jewell, Christopher M., additional, Gunderson, Andrew, additional, Boulmay, Brian, additional, Li, Rui, additional, Spieler, Bradley, additional, Happel, Kyle, additional, Feng, Zipei, additional, Dubay, Christopher, additional, Fisher, Brenda, additional, Aung, Sandra, additional, Mederos, Eileen, additional, Bifulco, Carlo B., additional, McNamara, Michael, additional, Bahjat, Keith, additional, Redmond, William, additional, Ochoa, Augusto, additional, Hu, Hong-Ming, additional, Mehta, Adi, additional, Lund-Johansen, Fridtjof, additional, Bedu-Addo, Frank, additional, Conn, Greg, additional, King, Michael, additional, Dutta, Panna, additional, Shepard, Robert, additional, Einstein, Mark, additional, Adams, Sylvia, additional, Wang, Ena, additional, Jin, Ping, additional, Novik, Yelena, additional, Morrison, Debra, additional, Oratz, Ruth, additional, Marincola, Franco M., additional, Stroncek, David, additional, Goldberg, Judith, additional, Formenti, Silvia C., additional, Galon, Jérôme, additional, Mlecnik, Bernhard, additional, Marliot, Florence, additional, Ou, Fang-Shu, additional, Lugli, Alessandro, additional, Zlobec, Inti, additional, Rau, Tilman T., additional, Nagtegaal, Iris D., additional, Vink-Borger, Elisa, additional, Hartmann, Arndt, additional, Geppert, Carol, additional, Roehrl, Michael H., additional, Bavi, Prashant, additional, Ohashi, Pamela S., additional, Wang, Julia Y., additional, Nguyen, Linh T., additional, Han, SeongJun, additional, MacGregor, Heather L., additional, Hafezi-Bakhtiari, Sara, additional, Wouters, Bradley G., additional, Kawakami, Yutaka, additional, Papivanova, Boryana, additional, Xu, Mingli, additional, Fujita, Tomonobu, additional, Hazama, Shoichi, additional, Suzuki, Nobuaki, additional, Nagano, Hiroaki, additional, Okuno, Kiyotaka, additional, Itoh, Kyogo, additional, Zavadova, Eva, additional, Vocka, Michal, additional, Spacek, Jan, additional, Petruzelka, Lubos, additional, Konopasek, Bohuslav, additional, Dundr, Pavel, additional, Skalova, Helena, additional, Torigoe, Toshihiko, additional, Sato, Noriyuki, additional, Furuhata, Tomohisa, additional, Takemasa, Ichiro, additional, Van den Eynde, Marc, additional, Jouret-Mourin, Anne, additional, Machiels, Jean-Pascal, additional, Fredriksen, Tessa, additional, Lafontaine, Lucie, additional, Buttard, Bénédicte, additional, Church, Sarah, additional, Maby, Pauline, additional, Angell, Helen, additional, Angelova, Mihaela, additional, Vasaturo, Angela, additional, Bindea, Gabriela, additional, Berger, Anne, additional, Lagorce, Christine, additional, Patel, Prabhu S., additional, Vora, Hemangini H., additional, Shah, Birva, additional, Patel, Jayendrakumar B., additional, Rajvik, Kruti N., additional, Pandya, Shashank J., additional, Shukla, Shilin N., additional, Wang, Yili, additional, Zhang, Guanjun, additional, Masucci, Giuseppe V., additional, Andersson, Emilia K., additional, Grizzi, Fabio, additional, Laghi, Luigi, additional, Botti, Gerardo, additional, Tatangelo, Fabiana, additional, Delrio, Paolo, additional, Cilberto, Gennaro, additional, Marincola, Franco, additional, Sargent, Daniel J., additional, Fox, Bernard A., additional, Algazi, Alain, additional, Tsai, Katy, additional, Rosenblum, Michael, additional, Nandoskar, Prachi, additional, Li, Amy, additional, Nonomura, John, additional, Takamura, Kathryn, additional, Dwyer, Mary, additional, Browning, Erica, additional, Talia, Reneta, additional, Twitty, Chris, additional, Gargosky, Sharron, additional, Campbell, Jean, additional, Le, Mai, additional, Pierce, Robert H., additional, Daud, Adil, additional, Gartrell, Robyn, additional, Marks, Douglas, additional, Stack, Edward, additional, Lu, Yan, additional, Izaki, Daisuke, additional, Beck, Kristen, additional, Jia, Dan Tong, additional, Armenta, Paul, additional, White-Stern, Ashley, additional, Fu, Yichun, additional, Blake, Zoe, additional, Taback, Bret, additional, Horst, Basil, additional, Saenger, Yvonne M., additional, Leonardo, Steven, additional, Gorden, Keith, additional, Fulton, Ross B., additional, Fraser, Kathryn, additional, Kangas, Takashi O., additional, Walsh, Richard, additional, Ertelt, Kathleen, additional, Graff, Jeremy, additional, Uhlik, Mark, additional, Sims, Jennifer S., additional, Lei, Liang, additional, Tsujiuchi, Takashi, additional, Bruce, Jeffrey N., additional, Canoll, Peter, additional, Tolcher, Anthony W, additional, Alley, Evan W, additional, Chichili, Gurunadh, additional, Canoll, Jan E, additional, Moore, Paul, additional, Bonvini, Ezio, additional, Johnson, Syd, additional, Shankar, Sadhna, additional, Vasselli, James, additional, Wigginton, Jon, additional, and Powderly, John, additional

Published
2016
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8. The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets

Author

Yang, Cliff Y, primary, Best, J Adam, additional, Knell, Jamie, additional, Yang, Edward, additional, Sheridan, Alison D, additional, Jesionek, Adam K, additional, Li, Haiyan S, additional, Rivera, Richard R, additional, Lind, Kristin Camfield, additional, D'Cruz, Louise M, additional, Watowich, Stephanie S, additional, Murre, Cornelis, additional, and Goldrath, Ananda W, additional

Published
2011
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11. ERAAP and Tapasin Independently Edit the Amino and Carboxyl Termini of MHC Class I Peptides.

Author

Takayuki Kanaseki, Lind, Kristin Camfield, Escobar, Hernando, Nagarajan, Niranjana, Reyes-Vargas, Eduardo, Rudd, Brant, Rockwood, Alan L., Van Kaer, Luc, Noriyuki Sato, Delgado, Julio C., and Shastri, Nilabh

Subjects
*ENDOPLASMIC reticulum, *AMINOPEPTIDASES, *ANTIGEN processing, *TAPASIN, *MAJOR histocompatibility complex, *AMINO acid sequence
Abstract

Effective CD8+ T cell responses depend on presentation of a stable peptide repertoire by MHC class I (MHC I) molecules on the cell surface. The overall quality of peptide-MHC I complexes (pMHC I) is determined by poorly understood mechanisms that generate and load peptides with appropriate consensus motifs onto MHC I. In this article, we show that both tapasin (Tpn), a key component of the peptide loading complex, and the endoplasmic reticulum aminopeptidase associated with Ag processing (ERAAP) are quintessential editors of distinct structural features of the peptide repertoire. We carried out reciprocal immunization of wild-type mice with cells from Tpn- or ERAAP-deficient mice. Specificity analysis of T cell responses showed that absence of Tpn or ERAAP independently altered the peptide repertoire by causing loss as well as gain of new pMHC I. Changes in amino acid sequences of MHC-bound peptides revealed that ERAAP and Tpn, respectively, defined the characteristic amino and carboxy termini of canonical MHC I peptides. Thus, the optimal pMHC I repertoire is produced by two distinct peptide editing steps in the endoplasmic reticulum. [ABSTRACT FROM AUTHOR]

Published
2013
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12. Loss of E protein transcription factors E2 A and HEB delays memory-precursor formation during the CD8+ T-cell immune response.

Author

D'Cruz, Louise M., Lind, Kristin Camfield, Wu, Bei Bei, Fujimoto, Jessica K., and Goldrath, Ananda W.

Abstract

The transcription factors E2 A and HEB (members of the E protein family) have been shown to play essential roles in lymphocyte development, while their negative regulators, the Id proteins, have been implicated in both lymphocyte development and in the CD8+ T-cell immune response. Here, we show that E proteins also influence CD8+ T cells responding to infection. E protein expression was upregulated by CD8+ T cells during the early stages of infection and increased E protein DNA-binding activity could be detected upon TCR stimulation. Deficiency in the E proteins, E2 A and HEB, led to increased frequency of terminally differentiated effector KLRG1hi CD8+ T cells in mice during infection, and decreased generation of longer-lived memory-precursor cells during the immune response. These data suggest a model whereby E protein transcription factor activity favors rapid memory-precursor T-cell formation while their negative regulators, Id2 and Id3, are both required for robust effector CD8+ T-cell response during infection. [ABSTRACT FROM AUTHOR]

Published
2012
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13. The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets.

Author

Yang, Cliff Y, Best, J Adam, Knell, Jamie, Yang, Edward, Sheridan, Alison D, Jesionek, Adam K, Li, Haiyan S, Rivera, Richard R, Lind, Kristin Camfield, D'Cruz, Louise M, Watowich, Stephanie S, Murre, Cornelis, and Goldrath, Ananda W

Subjects
TRANSCRIPTION factors, T cells, CYTOKINES, CELL receptors, GENE expression, IMMUNOLOGIC memory
Abstract

During infection, naive CD8+ T cells differentiate into effector cells, which are armed to eliminate pathogens, and memory cells, which are poised to protect against reinfection. The transcriptional program that regulates terminal differentiation into short-lived effector-memory versus long-lived memory cells is not clearly defined. Through the use of mice expressing reporters for the DNA-binding inhibitors Id2 and Id3, we identified Id3hi precursors of long-lived memory cells before the peak of T cell population expansion or upregulation of cell-surface receptors that indicate memory potential. Deficiency in Id2 or Id3 resulted in loss of distinct CD8+ effector and memory populations, which demonstrated unique roles for these inhibitors of E-protein transcription factors. Furthermore, cytokines altered the expression of Id2 and Id3 differently, which provides insight into how external cues influence gene expression. [ABSTRACT FROM AUTHOR]

Published
2011
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14. Acute GVHD, BK hemorrhagic cystitis and age are risk factors for transplant-associated thrombotic microangiopathy in adults

Author

Vasu, Sumithira, Bostic, Matthew, Zhao, Qiuhong, Sharma, Nidhi, Puto, Marcin, Knight, Samantha, Scott, Denise, Guzman, Rosalyn, Kromer, Meghan, Tackett, Karen, Lind, Kristin, Knill, Kathryn, Watson, Emily, Wall, Sarah, Saad, Ayman, Choe, Hannah, Larkin, Karilyn, Brammer, Jonathan, Jaglowski, Samantha, Penza, Sam, Davies, Stella M, and Cataland, Spero

Abstract

Hematopoietic cell transplantation associated thrombotic microangiopathy (TMA) is a complication associated with higher non-relapse mortality (NRM) in allogeneic transplant (HCT) patients. Current classification criteria are not generally agreed upon or validated, and presence of confounding factors post-transplant contribute to under-diagnosis or delayed diagnosis of TMA. We studied risk factors, incidence and biomarkersof TMA in 119 adult allogeneic HCT recipients.Twenty-seven patients developed clinically actionable phenotype of TMA (CA-TMA) and the incidence of CA-TMA was 22% by day 180. Among the 27 patients that developed CA-TMA, 10 patients developed CA-TMA prior to onset of acute graft-versus-host disease (aGVHD) and 17 patients developed CA-TMA after the onset of aGVHD. We report for the first time that age > 50, BK hemorrhagic cystitis) and other viral infections (CMV, HHV-6, Adenovirus) are risk factors for adult CA-TMA. Even after adjusting for aGVHD, CA-TMA was independently associated with significantly higher non-relapse mortality.These data illustrate relationships between CA-TMA and aGVHD, describe new risk factors for CA-TMA and emphasizes theneed to develop validated set of criteria for timely diagnosis.

Published
2021
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15. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): late breaking abstracts

Author

Althammer, Sonja, Steele, Keith, Rebelatto, Marlon, Tan, Tze Heng, Wiestler, Tobias, Schmidt, Guenter, Higgs, Brandon, Li, Xia, Shi, Li, Jin, Xiaoping, Antal, Joyce, Gupta, Ashok, Ranade, Koustubh, Binning, Gerd, Bellmunt, Joaquim, de Wit, Ronald, Vaughn, David J., Fradet, Yves, Lee, Jae Lyun, Fong, Lawrence, Vogelzang, Nicholas J., Climent, Miguel A., Petrylak, Daniel P., Choueiri, Toni K., Necchi, Andrea, Gerritsen, Winald, Gurney, Howard, Quinn, David I., Culine, Stéphane, Sternberg, Cora N., Mai, Yabing, Puhlmann, Markus, Perini, Rodolfo F., Bajorin, Dean F., Sharma, Padmanee, Callahan, Margaret K., Calvo, Emiliano, Kim, Joseph W., de Braud, Filipo, Ott, Patrick A., Bono, Petri, Pillai, Rathi N., Morse, Michael, Le, Dung T., Taylor, Matthew, Spilliopoulou, Pavlina, Bendell, Johanna, Jaeger, Dirk, Chan, Emily, Antonia, Scott J., Ascierto, Paolo A., Hennicken, Delphine, Tschaika, Marina, Azrilevich, Alex, Rosenberg, Jonathan, Levy, Ofer, Chan, Christopher, Cojocaru, Gady, Liang, Spencer, Ophir, Eran, Ganguly, Sudipto, Toporik, Amir, Kotturi, Maya, Kfir, Tal Fridman, Murter, Benjamin M., Logronio, Kathryn, Dassa, Liat, Leung, Ling, Greenwald, Shirley, Azulay, Meir, Kumar, Sandeep, Alteber, Zoya, Pan, Xiaoyu, Machlenkin, Arthur, Benita, Yair, Drake, Andrew W., Chajut, Ayelet, Salomon, Ran, Vankin, Ilan, Safyon, Einav, Hunter, John, Levine, Zurit, White, Mark, Leidner, Rom, Kang, Hyunseok, Haddad, Robert, Segal, Neil H., Wirth, Lori J., Ferris, Robert L., Hodi, F. Stephen, Sanborn, Rachel E., Gajewski, Thomas F., Sharfman, William, McDonald, Dan, Srivastava, Shivani, Gu, Xuemin, Phillips, Penny, Passey, Chaitali, Seiwert, Tanguy, Habtetsion, Tsadik, Zhou, Gang, Sakellariou-Thompson, Donastas, Haymaker, Cara, Creasy, Caitlin, Hurd, Mark, Uraoka, Naohiro, Canales, Jaime Rodriguez, Koptez, Scott, Hwu, Patrick, Maitra, Anirban, Bernatchez, Chantale, Coyle, Scott M., Roybel, Kole T., Rupp, Levi J., Santoro, Stephen P., Secrest, Stephanie, Spelman, Michael, Ho, Hanson, Gomes, Tina, Tse, Tiffany, Yung-Wu, Chia, Taunton, Jack, Lim, Wendell, Emtage, Peter, Moudgil, Tarsem, Ballesteros-Merino, Carmen, Hilton, Traci, Paustian, Christopher, Page, David, Urba, Walter, Fox, Bernard, Bell, Bryan, Patel, Ashish, Olafsen, Tove, Satpayev, Daulet, Torgov, Michael, Marchioni, Filippo, Romero, Jason, Jiang, Ziyue Karen, Zamilpa, Charles, Keppler, Jennifer S., Mascioni, Alessandro, Jia, Fang, Lee, Chen-Yu, Gudas, Jean, Sullivan, Ryan J., Hoshida, Yujin, Logan, Theodore, Khushalani, Nikhil, Giobbie-Hurder, Anita, Margolin, Kim, Roder, Joanna, Bhatt, Rupal, Koon, Henry, Olencki, Thomas, Hutson, Thomas, Curti, Brendan, Blackmon, Shauna, Mier, James W., Puzanov, Igor, Roder, Heinrich, Stewart, John, Amin, Asim, Ernstoff, Marc S., Clark, Joseph I., Atkins, Michael B., Kaufman, Howard L., Sosman, Jeffrey, Signoretti, Sabina, McDermott, David F., Anderson, Abraham A., Milhem, Mohammed M., Andtbacka, Robert H. I., Minor, David, Gorski, Kevin S., Baker, Daniel M., Hamid, Omid, Akporiaye, Emmanuel, Koguchi, Yoshinobu, Sutcliffe, Kim, Conder, Kristie, Marron, Thomas, Bhardwaj, Nina, Hammerich, Linda, George, Fiby, Kim-Schulze, Seunghee, Keler, Tibor, Davis, Tom, Crowley, Elizabeth, Salazar, Andres, Brody, Joshua, Monjazeb, Arta, Daly, Megan E., Riess, Jonathan, Li, Tianhong, Murphy, William J., Kelly, Karen, Hu, Zhiwei, Shen, Rulong, Campbell, Amanda, McMichael, Elizabeth, Yu, Lianbo, Ramaswam, Bhuvaneswari, London, Cheryl A., Xu, Tian, Carson, William, Kokolus, Kathleen M., Repasky, Elizabeth A., Schell, Todd D., Drabick, Joseph D., Messenheimer, David J., Jensen, Shawn, Rubinstein, Mark, Andrijauskaite, Kristina, Swiderska-syn, Marzena, Lind, Kristin, Choppin, Agnes, Roell, Marina K., Wrangle, John, Rhode, Peter, Wong, Hing, Ahmad, Shamim, Webb, Mason, Abu-Eid, Rasha, Shrimali, Rajeev, Verma, Vivek, Doroodchi, Atbin, Berrong, Zuzana, Yashar, David, Samara, Raed, Mkrtichyan, Mikayel, Khleif, Samir, Powell, Steven, Gitau, Mark, Sumey, Christopher, Terrell, Andrew, Lohr, Michele, Nowak, Ryan K., McGraw, Steven, Jensen, Ash, Blanchard, Miran, Gold, Kathryn A., Cohen, Ezra E. 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16. Loss of E protein transcription factors E2A and HEB delays memory-precursor formation during the CD8+ T-cell immune response.

Author

D'Cruz LM, Lind KC, Wu BB, Fujimoto JK, and Goldrath AW

Subjects
Animals, Basic Helix-Loop-Helix Transcription Factors deficiency, Basic Helix-Loop-Helix Transcription Factors genetics, CD8-Positive T-Lymphocytes metabolism, DNA-Binding Proteins biosynthesis, Immunologic Memory, Lectins, C-Type, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Immunologic biosynthesis, Basic Helix-Loop-Helix Transcription Factors metabolism, CD8-Positive T-Lymphocytes immunology, Inhibitor of Differentiation Protein 2 metabolism, Inhibitor of Differentiation Proteins metabolism
Abstract

The transcription factors E2A and HEB (members of the E protein family) have been shown to play essential roles in lymphocyte development, while their negative regulators, the Id proteins, have been implicated in both lymphocyte development and in the CD8(+) T-cell immune response. Here, we show that E proteins also influence CD8(+) T cells responding to infection. E protein expression was upregulated by CD8(+) T cells during the early stages of infection and increased E protein DNA-binding activity could be detected upon TCR stimulation. Deficiency in the E proteins, E2A and HEB, led to increased frequency of terminally differentiated effector KLRG1(hi) CD8(+) T cells in mice during infection, and decreased generation of longer-lived memory-precursor cells during the immune response. These data suggest a model whereby E protein transcription factor activity favors rapid memory-precursor T-cell formation while their negative regulators, Id2 and Id3, are both required for robust effector CD8(+) T-cell response during infection., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2012
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