J. Exp. Med., Volume 188, Number 11, December 7, 1998 1993-2005

Stability and Diversity of  T Cell Receptor Repertoire Usage during Lymphocytic Choriomeningitis Virus Infection of Mice

By Meei  Yun Lin and Raymond M. Welsh

From the Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School,  Worcester, Massachusetts 01655

Numerous studies have examined T cell receptor (TCR) usage of selected virus-specific T cell clones, yet little information is available regarding the stability and diversity of TCR repertoire usage during viral infections. Here, we analyzed the V8.1 TCR repertoire directly ex vivo by complementarity-determining region 3 (CDR3) length spectratyping throughout the acute lymphocytic choriomeningitis virus (LCMV) infection, into memory, and under conditions of T cell clonal exhaustion. The V8 population represented 30-35% of the LCMV-induced CD8⁺ T cells and included T cells recognizing several LCMV-encoded peptides, allowing for a comprehensive study of a multiclonal T cell response against a complex antigen. Genetically identical mice generated remarkably different T cell responses, as reflected by different spectratypes and different TCR sequences in same sized spectratype bands; however, a conserved CDR3 motif was found within some same sized bands. This indicated that meaningful studies on the evolution of the T cell repertoire required longitudinal studies within individual mice. Such longitudinal studies with peripheral blood lymphocyte samples showed that (a) the virus-induced T cell repertoire changes little during the apoptosis period after clearance of the viral antigens; (b) the LCMV infection dramatically skews the host T cell repertoire in the memory state; and (c) continuous selection of the T cell repertoire occurs under conditions of persistent infections.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Angelov, G. S., Guillaume, P., Luescher, I. F. (2009). CD8{beta} knockout mice mount normal anti-viral CD8+ T cell responses--but why?. Int Immunol 21: 123-135 [Abstract] [Full Text]  
• Motz, G. T., Eppert, B. L., Sun, G., Wesselkamper, S. C., Linke, M. J., Deka, R., Borchers, M. T. (2008). Persistence of Lung CD8 T Cell Oligoclonal Expansions upon Smoking Cessation in a Mouse Model of Cigarette Smoke-Induced Emphysema. J. Immunol. 181: 8036-8043 [Abstract] [Full Text]  
• Naumov, Y. N., Naumova, E. N., Yassai, M. B., Kota, K., Welsh, R. M., Selin, L. K. (2008). Multiple Glycines in TCR {alpha}-Chains Determine Clonally Diverse Nature of Human T Cell Memory to Influenza A Virus. J. Immunol. 181: 7407-7419 [Abstract] [Full Text]  
• Kedzierska, K., Venturi, V., Valkenburg, S. A., Davenport, M. P., Turner, S. J., Doherty, P. C. (2008). Homogenization of TCR Repertoires within Secondary CD62Lhigh and CD62Llow Virus-Specific CD8+ T Cell Populations. J. Immunol. 180: 7938-7947 [Abstract] [Full Text]  
• Curtis, J. L., Freeman, C. M., Hogg, J. C. (2007). The Immunopathogenesis of Chronic Obstructive Pulmonary Disease: Insights from Recent Research. Proc Am Thorac Soc 4: 512-521 [Abstract] [Full Text]  
• Almeida, J. R., Price, D. A., Papagno, L., Arkoub, Z. A., Sauce, D., Bornstein, E., Asher, T. E., Samri, A., Schnuriger, A., Theodorou, I., Costagliola, D., Rouzioux, C., Agut, H., Marcelin, A.-G., Douek, D., Autran, B., Appay, V. (2007). Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. JEM 204: 2473-2485 [Abstract] [Full Text]  
• Selin, L. K., Brehm, M. A. (2007). Frontiers in Nephrology: Heterologous Immunity, T Cell Cross-Reactivity, and Alloreactivity. J. Am. Soc. Nephrol. 18: 2268-2277 [Abstract] [Full Text]  
• Lichterfeld, M., Yu, X. G., Mui, S. K., Williams, K. L., Trocha, A., Brockman, M. A., Allgaier, R. L., Waring, M. T., Koibuchi, T., Johnston, M. N., Cohen, D., Allen, T. M., Rosenberg, E. S., Walker, B. D., Altfeld, M. (2007). Selective Depletion of High-Avidity Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ T Cells after Early HIV-1 Infection. J. Virol. 81: 4199-4214 [Abstract] [Full Text]  
• Wettstein, P. J., Strausbauch, M., Borson, N. (2007). Repertoires of T cell receptors expressed by graft-infiltrating T cells evolve during long-term recall responses to single minor histocompatibility antigens. Int Immunol 19: 523-534 [Abstract] [Full Text]  
• Ejrnaes, M., Filippi, C. M., Martinic, M. M., Ling, E. M., Togher, L. M., Crotty, S., von Herrath, M. G. (2006). Resolution of a chronic viral infection after interleukin-10 receptor blockade. JEM 203: 2461-2472 [Abstract] [Full Text]  
• Price, D. A., Brenchley, J. M., Ruff, L. E., Betts, M. R., Hill, B. J., Roederer, M., Koup, R. A., Migueles, S. A., Gostick, E., Wooldridge, L., Sewell, A. K., Connors, M., Douek, D. C. (2005). Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses. JEM 202: 1349-1361 [Abstract] [Full Text]  
• Lin, M. Y., Zal, T., Ch'en, I. L., Gascoigne, N. R. J., Hedrick, S. M. (2005). A Pivotal Role for the Multifunctional Calcium/Calmodulin-Dependent Protein Kinase II in T Cells: From Activation to Unresponsiveness. J. Immunol. 174: 5583-5592 [Abstract] [Full Text]  
• Kim, S.-K., Cornberg, M., Wang, X. Z., Chen, H. D., Selin, L. K., Welsh, R. M. (2005). Private specificities of CD8 T cell responses control patterns of heterologous immunity. JEM 201: 523-533 [Abstract] [Full Text]  
• Nussbaum, A. K., Whitton, J. L. (2004). The Contraction Phase of Virus-Specific CD8+ T Cells Is Unaffected by a Pan-Caspase Inhibitor. J. Immunol. 173: 6611-6618 [Abstract] [Full Text]  
• Junt, T., Scandella, E., Forster, R., Krebs, P., Krautwald, S., Lipp, M., Hengartner, H., Ludewig, B. (2004). Impact of CCR7 on Priming and Distribution of Antiviral Effector and Memory CTL. J. Immunol. 173: 6684-6693 [Abstract] [Full Text]  
• Zhong, W., Reinherz, E. L. (2004). In vivo selection of a TCR V{beta} repertoire directed against an immunodominant influenza virus CTL epitope. Int Immunol 16: 1549-1559 [Abstract] [Full Text]  
• Oh, S., Perera, L. P., Burke, D. S., Waldmann, T. A., Berzofsky, J. A. (2004). IL-15/IL-15R{alpha}-mediated avidity maturation of memory CD8+ T cells. Proc. Natl. Acad. Sci. USA 101: 15154-15159 [Abstract] [Full Text]  
• Boudinot, P., Bernard, D., Boubekeur, S., Thoulouze, M.-I., Bremont, M., Benmansour, A. (2004). The glycoprotein of a fish rhabdovirus profiles the virus-specific T-cell repertoire in rainbow trout. J. Gen. Virol. 85: 3099-3108 [Abstract] [Full Text]  
• Liu, F., Whitton, J. L., Slifka, M. K. (2004). The Rapidity with Which Virus-Specific CD8+ T Cells Initiate IFN-{gamma} Synthesis Increases Markedly over the Course of Infection and Correlates with Immunodominance. J. Immunol. 173: 456-462 [Abstract] [Full Text]  
• Kedzierska, K., Turner, S. J., Doherty, P. C. (2004). Conserved T cell receptor usage in primary and recall responses to an immunodominant influenza virus nucleoprotein epitope. Proc. Natl. Acad. Sci. USA 101: 4942-4947 [Abstract] [Full Text]  
• Nishio, J., Suzuki, M., Nanki, T., Miyasaka, N., Kohsaka, H. (2004). Development of TCRB CDR3 length repertoire of human T lymphocytes. Int Immunol 16: 423-431 [Abstract] [Full Text]  
• Kassiotis, G., Zamoyska, R., Stockinger, B. (2003). Involvement of Avidity for Major Histocompatibility Complex in Homeostasis of Naive and Memory T Cells. JEM 197: 1007-1016 [Abstract] [Full Text]  
• Slifka, M. K., Blattman, J. N., Sourdive, D. J. D., Liu, F., Huffman, D. L., Wolfe, T., Hughes, A., Oldstone, M. B. A., Ahmed, R., von Herrath, M. G. (2003). Preferential Escape of Subdominant CD8+ T Cells During Negative Selection Results in an Altered Antiviral T Cell Hierarchy. J. Immunol. 170: 1231-1239 [Abstract] [Full Text]  
• Fuller, M. J., Zajac, A. J. (2003). Ablation of CD8 and CD4 T Cell Responses by High Viral Loads. J. Immunol. 170: 477-486 [Abstract] [Full Text]  
• Kim, S.-K., Brehm, M. A., Welsh, R. M., Selin, L. K. (2002). Dynamics of Memory T Cell Proliferation Under Conditions of Heterologous Immunity and Bystander Stimulation. J. Immunol. 169: 90-98 [Abstract] [Full Text]  
• Blattman, J. N., Antia, R., Sourdive, D. J.D., Wang, X., Kaech, S. M., Murali-Krishna, K., Altman, J. D., Ahmed, R. (2002). Estimating the Precursor Frequency of Naive Antigen-specific CD8 T Cells. JEM 195: 657-664 [Abstract] [Full Text]  
• Holtappels, R., Thomas, D., Podlech, J., Reddehase, M. J. (2002). Two Antigenic Peptides from Genes m123 and m164 of Murine Cytomegalovirus Quantitatively Dominate CD8 T-Cell Memory in the H-2d Haplotype. J. Virol. 76: 151-164 [Abstract] [Full Text]  
• Boudinot, P., Boubekeur, S., Benmansour, A. (2001). Rhabdovirus Infection Induces Public and Private T Cell Responses in Teleost Fish. J. Immunol. 167: 6202-6209 [Abstract] [Full Text]  
• Baron, C., McMorrow, I., Sachs, D. H, LeGuern, C. (2001). Persistence of Dominant T Cell Clones in Accepted Solid Organ Transplants. J. Immunol. 167: 4154-4160 [Abstract] [Full Text]  
• Nishio, J., Suzuki, M., Miyasaka, N., Kohsaka, H. (2001). Clonal Biases of Peripheral CD8 T Cell Repertoire Directly Reflect Local Inflammation in Polymyositis. J. Immunol. 167: 4051-4058 [Abstract] [Full Text]  
• McNally, J. M., Zarozinski, C. C., Lin, M.-Y., Brehm, M. A., Chen, H. D., Welsh, R. M. (2001). Attrition of Bystander CD8 T Cells during Virus-Induced T-Cell and Interferon Responses. J. Virol. 75: 5965-5976 [Abstract] [Full Text]  
• Haring, J. S., Pewe, L. L., Perlman, S. (2001). High-Magnitude, Virus-Specific CD4 T-Cell Response in the Central Nervous System of Coronavirus-Infected Mice. J. Virol. 75: 3043-3047 [Abstract] [Full Text]  
• Gozalo-Sanmillan, S., McNally, J. M., Lin, M. Y., Chambers, C. A., Berg, L. J. (2001). Cutting Edge: Two Distinct Mechanisms Lead to Impaired T Cell Homeostasis in Janus Kinase 3- and CTLA-4-Deficient Mice. J. Immunol. 166: 727-730 [Abstract] [Full Text]  
• Blattman, J. N., Sourdive, D. J. D., Murali-Krishna, K., Ahmed, R., Altman, J. D. (2000). Evolution of the T Cell Repertoire During Primary, Memory, and Recall Responses to Viral Infection. J. Immunol. 165: 6081-6090 [Abstract] [Full Text]  
• Annels, N. E., Callan, M. F. C., Tan, L., Rickinson, A. B. (2000). Changing Patterns of Dominant TCR Usage with Maturation of an EBV-Specific Cytotoxic T Cell Response. J. Immunol. 165: 4831-4841 [Abstract] [Full Text]  
• Hassett, D. E., Slifka, M. K., Zhang, J., Whitton, J. L. (2000). Direct Ex Vivo Kinetic and Phenotypic Analyses of CD8+ T-Cell Responses Induced by DNA Immunization. J. Virol. 74: 8286-8291 [Abstract] [Full Text]  
• Peacock, C. D., Lin, M. Y., Ortaldo, J. R., Welsh, R. M. (2000). The Virus-Specific and Allospecific Cytotoxic T-Lymphocyte Response to Lymphocytic Choriomeningitis Virus Is Modified in a Subpopulation of CD8+ T Cells Coexpressing the Inhibitory Major Histocompatibility Complex Class I Receptor Ly49G2. J. Virol. 74: 7032-7038 [Abstract] [Full Text]  
• Hardy, C. L., Silins, S. L., Woodland, David. L., Blackman, M. A. (2000). Murine {gamma}-herpesvirus infection causes V{beta}4-specific CDR3-restricted clonal expansions within CD8+ peripheral blood T lymphocytes. Int Immunol 12: 1193-1204 [Abstract] [Full Text]  
• Kang, J.-A., Mohindru, M., Kang, B.-S., Park, S. H., Kim, B. S. (2000). Clonal Expansion of Infiltrating T Cells in the Spinal Cords of SJL/J Mice Infected with Theiler's Virus. J. Immunol. 165: 583-590 [Abstract] [Full Text]  
• Harrington, L. E., Galvan, M., Baum, L. G., Altman, J. D., Ahmed, R. (2000). Differentiating between Memory and Effector CD8 T Cells by Altered Expression of Cell Surface O-Glycans. JEM 191: 1241-1246 [Abstract] [Full Text]  
• Arstila, T., Arstila, T. P., Calbo, S., Selz, F., Malassis-Seris, M., Vassalli, P., Kourilsky, P., Guy-Grand, D. (2000). Identical T Cell Clones Are Located within the Mouse Gut Epithelium and Lamina Propria and Circulate in the Thoracic Duct Lymph. JEM 191: 823-834 [Abstract] [Full Text]  
• Slifka, M. K., Pagarigan, R. R., Whitton, J. L. (2000). NK Markers Are Expressed on a High Percentage of Virus-Specific CD8+ and CD4+ T Cells. J. Immunol. 164: 2009-2015 [Abstract] [Full Text]  
• Pewe, L., Heard, S. B., Bergmann, C., Dailey, M. O., Perlman, S. (1999). Selection of CTL Escape Mutants in Mice Infected with a Neurotropic Coronavirus: Quantitative Estimate of TCR Diversity in the Infected Central Nervous System. J. Immunol. 163: 6106-6113 [Abstract] [Full Text]  
• Brawand, P., Cerottini, J.-C., MacDonald, H. R. (1999). Hierarchal Utilization of Different T-Cell Receptor Vbeta Gene Segments in the CD8+-T-Cell Response to an Immunodominant Moloney Leukemia Virus-Encoded Epitope In Vivo. J. Virol. 73: 9161-9169 [Abstract] [Full Text]  
• Wherry, E. J., Puorro, K. A., Porgador, A., Eisenlohr, L. C. (1999). The Induction of Virus-Specific CTL as a Function of Increasing Epitope Expression: Responses Rise Steadily Until Excessively High Levels of Epitope Are Attained. J. Immunol. 163: 3735-3745 [Abstract] [Full Text]  
• Reignat, S., Webster, G. J.M., Brown, D., Ogg, G. S., King, A., Seneviratne, S. L., Dusheiko, G., Williams, R., Maini, M. K., Bertoletti, A. (2002). Escaping High Viral Load Exhaustion: CD8 Cells with Altered Tetramer Binding in Chronic Hepatitis B Virus Infection. JEM 195: 1089-1101 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS