J. Exp. Med., Volume 187, Number 9, May 4, 1998 1383-1393

Induction and Exhaustion of Lymphocytic Choriomeningitis Virus-specific Cytotoxic T Lymphocytes Visualized Using Soluble Tetrameric Major Histocompatibility Complex Class I-Peptide Complexes

By Awen Gallimore,^* Ann Glithero, Andrew Godkin, Alain C. Tissot,^§ Andreas Plückthun,^§ Tim Elliott, Hans Hengartner,^* and Rolf Zinkernagel^*

From the ^* Institute of Experimental Immunology, CH-8091, Zürich, Switzerland; the  Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX39DU, United Kingdom; and the ^§ Biochemische Institut, 8057, Zürich, Switzerland

This study describes the construction of soluble major histocompatibility complexes consisting of the mouse class I molecule, H-2D^b, chemically biotinylated 2 microglobulin and a peptide epitope derived from the glycoprotein (GP; amino acids 33-41) of lymphocytic choriomeningitis virus (LCMV). Tetrameric class I complexes, which were produced by mixing the class I complexes with phycoerythrin-labeled neutravidin, permitted direct analysis of virus-specific cytotoxic T lymphocytes (CTLs) by flow cytometry. This technique was validated by (a) staining CD8⁺ cells in the spleens of transgenic mice that express a T cell receptor (TCR) specific for H-2D^b in association with peptide GP33-41, and (b) by staining virus-specific CTLs in the cerebrospinal fluid of C57BL/6 (B6) mice that had been infected intracranially with LCMV-DOCILE. Staining of spleen cells isolated from B6 mice revealed that up to 40% of CD8⁺ T cells were GP33 tetramer⁺ during the initial phase of LCMV infection. In contrast, GP33 tetramers did not stain CD8⁺ T cells isolated from the spleens of B6 mice that had been infected 2 mo previously with LCMV above the background levels found in naive mice. The fate of virus-specific CTLs was analyzed during the acute phase of infection in mice challenged both intracranially and intravenously with a high or low dose of LCMV-DOCILE. The results of the study show that the outcome of infection by LCMV is determined by antigen load alone. Furthermore, the data indicate that deletion of virus-specific CTLs in the presence of excessive antigen is preceded by TCR downregulation and is dependent upon perforin.

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• Ciurea, A., Hunziker, L., Klenerman, P., Hengartner, H., Zinkernagel, R. M. (2001). Impairment of CD4+ T Cell Responses during Chronic Virus Infection Prevents Neutralizing Antibody Responses against Virus Escape Mutants. J. Exp. Med. 193: 297-306 [Abstract] [Full Text]  
• Goulder, P. J.R., Altfeld, M. A., Rosenberg, E. S., Nguyen, T., Tang, Y., Eldridge, R. L., Addo, M. M., He, S., Mukherjee, J. S., Phillips, M. N., Bunce, M., Kalams, S. A., Sekaly, R. P., Walker, B. D., Brander, C. (2001). Substantial Differences in Specificity of HIV-specific Cytotoxic T Cells in Acute and Chronic HIV Infection. J. Exp. Med. 193: 181-194 [Abstract] [Full Text]  
• Goulder, P. J.R., Tang, Y., Brander, C., Betts, M. R., Altfeld, M., Annamalai, K., Trocha, A., He, S., Rosenberg, E. S., Ogg, G., O'Callaghan, C. A., Kalams, S. A., McKinney, R. E. , Jr., Mayer, K., Koup, R. A., Pelton, S. I., Burchett, S. K., McIntosh, K., Walker, B. D. (2000). Functionally Inert HIV-specific Cytotoxic T Lymphocytes Do Not Play a Major Role in Chronically Infected Adults and Children. J. Exp. Med. 192: 1819-1832 [Abstract] [Full Text]  
• Santra, S., Barouch, D. H., Jackson, S. S., Kuroda, M. J., Schmitz, J. E., Lifton, M. A., Sharpe, A. H., Letvin, N. L. (2000). Functional Equivalency of B7-1 and B7-2 for Costimulating Plasmid DNA Vaccine-Elicited CTL Responses. J. Immunol. 165: 6791-6795 [Abstract] [Full Text]  
• Mercado, R., Vijh, S., Allen, S. E., Kerksiek, K., Pilip, I. M., Pamer, E. G. (2000). Early Programming of T Cell Populations Responding to Bacterial Infection. J. Immunol. 165: 6833-6839 [Abstract] [Full Text]  
• Reichstetter, S., Ettinger, R. A., Liu, A. W., Gebe, J. A., Nepom, G. T., Kwok, W. W. (2000). Distinct T Cell Interactions with HLA Class II Tetramers Characterize a Spectrum of TCR Affinities in the Human Antigen-Specific T Cell Response. J. Immunol. 165: 6994-6998 [Abstract] [Full Text]  
• Badovinac, V. P., Tvinnereim, A. R., Harty, J. T. (2000). Regulation of Antigen-Specific CD8+ T Cell Homeostasis by Perforin and Interferon-gamma. Science 290: 1354-1357 [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]  
• Zavazava, N., Kabelitz, D. (2000). Alloreactivity and apoptosis in graft rejection and transplantation tolerance. J. Leukoc. Biol. 68: 167-174 [Abstract] [Full Text]  
• Mollet, L., Li, T.-S., Samri, A., Tournay, C., Tubiana, R., Calvez, V., Debre, P., Katlama, C., Autran, B. (2000). Dynamics of HIV-Specific CD8+ T Lymphocytes with Changes in Viral Load. J. Immunol. 165: 1692-1704 [Abstract] [Full Text]  
• Trimble, L. A., Kam, L. W., Friedman, R. S., Xu, Z., Lieberman, J. (2000). CD3zeta and CD28 down-modulation on CD8 T cells during viral infection. Blood 96: 1021-1029 [Abstract] [Full Text]  
• Kopf, M., Coyle, A. J., Schmitz, N., Barner, M., Oxenius, A., Gallimore, A., Gutierrez-Ramos, J.-C., Bachmann, M. F. (2000). Inducible Costimulator Protein (ICOS) Controls T Helper Cell Subset Polarization after Virus and Parasite Infection. J. Exp. Med. 192: 53-62 [Abstract] [Full Text]  
• Appay, V., Nixon, D. F., Donahoe, S. M., Gillespie, G. M.A., Dong, T., King, A., Ogg, G. S., Spiegel, H. M.L., Conlon, C., Spina, C. A., Havlir, D. V., Richman, D. D., Waters, A., Easterbrook, P., McMichael, A. J., Rowland-Jones, S. L. (2000). HIV-specific CD8+ T Cells Produce Antiviral Cytokines but Are Impaired in Cytolytic Function. J. Exp. Med. 192: 63-76 [Abstract] [Full Text]  
• Goulder, P. J. R., Tang, Y., Pelton, S. I., Walker, B. D. (2000). HLA-B57-Restricted Cytotoxic T-Lymphocyte Activity in a Single Infected Subject toward Two Optimal Epitopes, One of Which Is Entirely Contained within the Other. J. Virol. 74: 5291-5299 [Abstract] [Full Text]  
• Spencer, J. V., Braciale, T. J. (2000). Incomplete CD8+ T Lymphocyte Differentiation as a Mechanism for Subdominant Cytotoxic T Lymphocyte Responses to a Viral Antigen. J. Exp. Med. 191: 1687-1698 [Abstract] [Full Text]  
• Lechner, F., Wong, D. K.H., Dunbar, P. R., Chapman, R., Chung, R. T., Dohrenwend, P., Robbins, G., Phillips, R., Klenerman, P., Walker, B. D. (2000). Analysis of Successful Immune Responses in Persons Infected with Hepatitis C Virus. J. Exp. Med. 191: 1499-1512 [Abstract] [Full Text]  
• Marten, N. W., Stohlman, S. A., Atkinson, R. D., Hinton, D. R., Fleming, J. O., Bergmann, C. C. (2000). Contributions of CD8+ T Cells and Viral Spread to Demyelinating Disease. J. Immunol. 164: 4080-4088 [Abstract] [Full Text]  
• Kwok, W. W., Liu, A. W., Novak, E. J., Gebe, J. A., Ettinger, R. A., Nepom, G. T., Reymond, S. N., Koelle, D. M. (2000). HLA-DQ Tetramers Identify Epitope-Specific T Cells in Peripheral Blood of Herpes Simplex Virus Type 2-Infected Individuals: Direct Detection of Immunodominant Antigen-Responsive Cells. J. Immunol. 164: 4244-4249 [Abstract] [Full Text]  

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