J. Exp. Med., Volume 188, Number 4, August 17, 1998 785-790

Oligoclonal Expansions of CD8⁺ T Cells in Chronic HIV Infection Are Antigen Specific

By Jamie D.K. Wilson, Graham S. Ogg, Rachel L. Allen, Philip J.R. Goulder, Anthony Kelleher, Andy K. Sewell, Christopher A. O'Callaghan, Sarah L. Rowland-Jones, Margaret F.C. Callan, and Andrew J. McMichael

From the Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom

Acute HIV infection is associated with a vigorous immune response characterized by the proliferation of selected T cell receptor V beta (BV)-expressing CD8⁺ T cells. These `expansions', which are commonly detected in the peripheral blood, can persist during chronic HIV infection and may result in the dominance of particular clones. Such clonal populations are most consistent with antigen-driven expansions of CD8⁺ T cells. However, due to the difficulties in studying antigen-specific T cells in vivo, it has been hard to prove that oligoclonal BV expansions are actually HIV specific. The use of tetrameric major histocompatibility complex-peptide complexes has recently enabled direct visualization of antigen-specific T cells ex vivo but has not provided information on their clonal composition. We have now made use of these tetrameric complexes in conjunction with anti-BV chain-specific monoclonal antibodies and analysis of cytotoxic T lymphocyte lines/clones to show that chronically clonally expanded CD8⁺ T cells are HIV specific in vivo.

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

This article has been cited by other articles:

• Turnbull, E. L., Wong, M., Wang, S., Wei, X., Jones, N. A., Conrod, K. E., Aldam, D., Turner, J., Pellegrino, P., Keele, B. F., Williams, I., Shaw, G. M., Borrow, P. (2009). Kinetics of Expansion of Epitope-Specific T Cell Responses during Primary HIV-1 Infection. J. Immunol. 182: 7131-7145 [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]  
• Yang, H., Dong, T., Turnbull, E., Ranasinghe, S., Ondondo, B., Goonetilleke, N., Winstone, N., di Gleria, K., Bowness, P., Conlon, C., Borrow, P., Hanke, T., McMichael, A., Dorrell, L. (2007). Broad TCR Usage in Functional HIV-1-Specific CD8+ T Cell Expansions Driven by Vaccination during Highly Active Antiretroviral Therapy. J. Immunol. 179: 597-606 [Abstract] [Full Text]  
• Gillespie, G. M. A., Stewart-Jones, G., Rengasamy, J., Beattie, T., Bwayo, Job. J., Plummer, F. A., Kaul, R., McMichael, A. J., Easterbrook, P., Dong, T., Jones, E. Y., Rowland-Jones, S. L. (2006). Strong TCR Conservation and Altered T Cell Cross-Reactivity Characterize a B*57-Restricted Immune Response in HIV-1 Infection. J. Immunol. 177: 3893-3902 [Abstract] [Full Text]  
• Neveu, B., Echasserieau, K., Hill, T., Kuus-Reichel, K., Houssaint, E., Bonneville, M., Saulquin, X. (2006). Impact of CD8-MHC class I interaction in detection and sorting efficiencies of antigen-specific T cells using MHC class I/peptide multimers: contribution of pMHC valency. Int Immunol 18: 1139-1145 [Abstract] [Full Text]  
• Turnbull, E. L., Lopes, A. R., Jones, N. A., Cornforth, D., Newton, P., Aldam, D., Pellegrino, P., Turner, J., Williams, I., Wilson, C. M., Goepfert, P. A., Maini, M. K., Borrow, P. (2006). HIV-1 Epitope-Specific CD8+ T Cell Responses Strongly Associated with Delayed Disease Progression Cross-Recognize Epitope Variants Efficiently. J. Immunol. 176: 6130-6146 [Abstract] [Full Text]  
• Meyer-Olson, D., Brady, K. W., Bartman, M. T., O'Sullivan, K. M., Simons, B. C., Conrad, J. A., Duncan, C. B., Lorey, S., Siddique, A., Draenert, R., Addo, M., Altfeld, M., Rosenberg, E., Allen, T. M., Walker, B. D., Kalams, S. A. (2006). Fluctuations of functionally distinct CD8+ T-cell clonotypes demonstrate flexibility of the HIV-specific TCR repertoire. Blood 107: 2373-2383 [Abstract] [Full Text]  
• Wooldridge, L., van den Berg, H. A., Glick, M., Gostick, E., Laugel, B., Hutchinson, S. L., Milicic, A., Brenchley, J. M., Douek, D. C., Price, D. A., Sewell, A. K. (2005). Interaction between the CD8 Coreceptor and Major Histocompatibility Complex Class I Stabilizes T Cell Receptor-Antigen Complexes at the Cell Surface. J. Biol. Chem. 280: 27491-27501 [Abstract] [Full Text]  
• Tynan, F. E., Borg, N. A., Miles, J. J., Beddoe, T., El-Hassen, D., Silins, S. L., van Zuylen, W. J. M., Purcell, A. W., Kjer-Nielsen, L., McCluskey, J., Burrows, S. R., Rossjohn, J. (2005). High Resolution Structures of Highly Bulged Viral Epitopes Bound to Major Histocompatibility Complex Class I: IMPLICATIONS FOR T-CELL RECEPTOR ENGAGEMENT AND T-CELL IMMUNODOMINANCE. J. Biol. Chem. 280: 23900-23909 [Abstract] [Full Text]  
• Tully, G., Kortsik, C., Hohn, H., Zehbe, I., Hitzler, W. E., Neukirch, C., Freitag, K., Kayser, K., Maeurer, M. J. (2005). Highly Focused T Cell Responses in Latent Human Pulmonary Mycobacterium tuberculosis Infection. J. Immunol. 174: 2174-2184 [Abstract] [Full Text]  
• Dong, T., Stewart-Jones, G., Chen, N., Easterbrook, P., Xu, X., Papagno, L., Appay, V., Weekes, M., Conlon, C., Spina, C., Little, S., Screaton, G., van der Merwe, A., Richman, D. D., McMichael, A. J., Jones, E. Y., Rowland-Jones, S. L. (2004). HIV-specific Cytotoxic T Cells from Long-Term Survivors Select a Unique T Cell Receptor. JEM 200: 1547-1557 [Abstract] [Full Text]  
• Kan-Mitchell, J., Bisikirska, B., Wong-Staal, F., Schaubert, K. L., Bajcz, M., Bereta, M. (2004). The HIV-1 HLA-A2-SLYNTVATL Is a Help-Independent CTL Epitope. J. Immunol. 172: 5249-5261 [Abstract] [Full Text]  
• Lopes, A. R., Jaye, A., Dorrell, L., Sabally, S., Alabi, A., Jones, N. A., Flower, D. R., De Groot, A., Newton, P., Lascar, R. M., Williams, I., Whittle, H., Bertoletti, A., Borrow, P., Maini, M. K. (2003). Greater CD8+ TCR Heterogeneity and Functional Flexibility in HIV-2 Compared to HIV-1 Infection. J. Immunol. 171: 307-316 [Abstract] [Full Text]  
• Kharbanda, M., McCloskey, T. W., Pahwa, R., Sun, M., Pahwa, S. (2003). Alterations in T-Cell Receptor V{beta} Repertoire of CD4 and CD8 T Lymphocytes in Human Immunodeficiency Virus-Infected Children. CVI 10: 53-58 [Abstract] [Full Text]  
• Serra, P., Amrani, A., Han, B., Yamanouchi, J., Thiessen, S. J., Santamaria, P. (2002). RAG-dependent peripheral T cell receptor diversification in CD8+ T lymphocytes. Proc. Natl. Acad. Sci. USA 99: 15566-15571 [Abstract] [Full Text]  
• Caulfield, M. J., Wang, S., Smith, J. G., Tobery, T. W., Liu, X., Davies, M.-E., Casimiro, D. R., Fu, T.-M., Simon, A., Evans, R. K., Emini, E. A., Shiver, J. (2002). Sustained Peptide-Specific Gamma Interferon T-Cell Response in Rhesus Macaques Immunized with Human Immunodeficiency Virus gag DNA Vaccines. J. Virol. 76: 10038-10043 [Abstract] [Full Text]  
• Douek, D. C., Betts, M. R., Brenchley, J. M., Hill, B. J., Ambrozak, D. R., Ngai, K.-L., Karandikar, N. J., Casazza, J. P., Koup, R. A. (2002). A Novel Approach to the Analysis of Specificity, Clonality, and Frequency of HIV-Specific T Cell Responses Reveals a Potential Mechanism for Control of Viral Escape. J. Immunol. 168: 3099-3104 [Abstract] [Full Text]  
• Pilch, H., Hohn, H., Freitag, K., Neukirch, C., Necker, A., Haddad, P., Tanner, B., Knapstein, P. G., Maeurer, M. J. (2002). Improved Assessment of T-Cell Receptor (TCR) VB Repertoire in Clinical Specimens: Combination of TCR-CDR3 Spectratyping with Flow Cytometry-Based TCR VB Frequency Analysis. CVI 9: 257-266 [Abstract] [Full Text]  
• Garba, M. L., Pilcher, C. D., Bingham, A. L., Eron, J., Frelinger, J. A. (2002). HIV Antigens Can Induce TGF-{beta}1-Producing Immunoregulatory CD8+ T Cells. J. Immunol. 168: 2247-2254 [Abstract] [Full Text]  
• KUROSU, K., YUMOTO, N., ROM, W. N., TAKIGUCHI, Y., JAISHREE, J., NAKATA, K., TATSUMI, K., MIKATA, A., KURIYAMA, T., WEIDEN, M. D. (2002). Oligoclonal T Cell Expansions in Pulmonary Lymphoproliferative Disorders . Demonstration of the Frequent Occurrence of Oligoclonal T Cells in Human Immunodeficiency Virus-Related Lymphoid Interstitial Pneumonia. Am. J. Respir. Crit. Care Med. 165: 254-259 [Abstract] [Full Text]  
• Morice, W. G., Kurtin, P. J., Tefferi, A., Hanson, C. A. (2002). Distinct bone marrow findings in T-cell granular lymphocytic leukemia revealed by paraffin section immunoperoxidase stains for CD8, TIA-1, and granzyme B. Blood 99: 268-274 [Abstract] [Full Text]  
• Silins, S. L., Sherritt, M. A., Silleri, J. M., Cross, S. M., Elliott, S. L., Bharadwaj, M., Le, T. T. T., Morrison, L. E., Khanna, R., Moss, D. J., Suhrbier, A., Misko, I. S. (2001). Asymptomatic primary Epstein-Barr virus infection occurs in the absence of blood T-cell repertoire perturbations despite high levels of systemic viral load. Blood 98: 3739-3744 [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]  
• Coulie, P. G., Karanikas, V., Colau, D., Lurquin, C., Landry, C., Marchand, M., Dorval, T., Brichard, V., Boon, T. (2001). A monoclonal cytolytic T-lymphocyte response observed in a melanoma patient vaccinated with a tumor-specific antigenic peptide encoded by gene MAGE-3. Proc. Natl. Acad. Sci. USA 10.1073/pnas.161260098v1 [Abstract] [Full Text]  
• Bitmansour, A. D., Waldrop, S. L., Pitcher, C. J., Khatamzas, E., Kern, F., Maino, V. C., Picker, L. J. (2001). Clonotypic Structure of the Human CD4+ Memory T Cell Response to Cytomegalovirus. J. Immunol. 167: 1151-1163 [Abstract] [Full Text]  
• Amrani, A., Serra, P., Yamanouchi, J., Trudeau, J. D., Tan, R., Elliott, J. F., Santamaria, P. (2001). Expansion of the Antigenic Repertoire of a Single T Cell Receptor upon T Cell Activation. J. Immunol. 167: 655-666 [Abstract] [Full Text]  
• Dobrzanski, M. J., Reome, J. B., Dutton, R. W. (2001). Role of Effector Cell-Derived IL-4, IL-5, and Perforin in Early and Late Stages of Type 2 CD8 Effector Cell-Mediated Tumor Rejection. J. Immunol. 167: 424-434 [Abstract] [Full Text]  
• Novak, E. J., Liu, A. W., Gebe, J. A., Falk, B. A., Nepom, G. T., Koelle, D. M., Kwok, W. W. (2001). Tetramer-Guided Epitope Mapping: Rapid Identification and Characterization of Immunodominant CD4+ T Cell Epitopes from Complex Antigens. J. Immunol. 166: 6665-6670 [Abstract] [Full Text]  
• Chen, Z. W., Li, Y., Zeng, X., Kuroda, M. J., Schmitz, J. E., Shen, Y., Lai, X., Shen, L., Letvin, N. L. (2001). The TCR Repertoire of an Immunodominant CD8+ T Lymphocyte Population. J. Immunol. 166: 4525-4533 [Abstract] [Full Text]  
• Gorochov, G., Neumann, A. U., Parizot, C., Li, T., Katlama, C., Debre, P. (2001). Down-regulation of CD8+ T-cell expansions in patients with human immunodeficiency virus infection receiving highly active combination therapy. Blood 97: 1787-1795 [Abstract] [Full Text]  
• Vogel, T. U., Allen, T. M., Altman, J. D., Watkins, D. I. (2001). Functional Impairment of Simian Immunodeficiency Virus-Specific CD8+ T Cells during the Chronic Phase of Infection. J. Virol. 75: 2458-2461 [Abstract] [Full Text]  
• Schito, A. M., Vittinghoff, E., Hecht, F. M., Elkins, M. K., Kahn, J. O., Levy, J. A., Oksenberg, J. R. (2001). Longitudinal analysis of T-cell receptor gene use by CD8+ T cells in early human immunodeficiency virus infection in patients receiving highly active antiretroviral therapy. Blood 97: 214-220 [Abstract] [Full Text]  
• Lim, D.-G., Bieganowska Bourcier, K., Freeman, G. J., Hafler, D. A. (2000). Examination of CD8+ T Cell Function in Humans Using MHC Class I Tetramers: Similar Cytotoxicity but Variable Proliferation and Cytokine Production Among Different Clonal CD8+ T Cells Specific to a Single Viral Epitope. J. Immunol. 165: 6214-6220 [Abstract] [Full Text]  
• Kou, Z. C., Puhr, J. S., Rojas, M., McCormack, W. T., Goodenow, M. M., Sleasman, J. W. (2000). T-Cell Receptor Vbeta Repertoire CDR3 Length Diversity Differs within CD45RA and CD45RO T-Cell Subsets in Healthy and Human Immunodeficiency Virus-Infected Children. CVI 7: 953-959 [Abstract] [Full Text]  
• Gillespie, G. M. A., Wills, M. R., Appay, V., O'Callaghan, C., Murphy, M., Smith, N., Sissons, P., Rowland-Jones, S., Bell, J. I., Moss, P. A. H. (2000). Functional Heterogeneity and High Frequencies of Cytomegalovirus-Specific CD8+ T Lymphocytes in Healthy Seropositive Donors. J. Virol. 74: 8140-8150 [Abstract] [Full Text]  
• Gea-Banacloche, J. C., Migueles, S. A., Martino, L., Shupert, W. L., McNeil, A. C., Sabbaghian, M. S., Ehler, L., Prussin, C., Stevens, R., Lambert, L., Altman, J., Hallahan, C. W., de Quiros, J. C. L. B., Connors, M. (2000). Maintenance of Large Numbers of Virus-Specific CD8+ T Cells in HIV-Infected Progressors and Long-Term Nonprogressors. J. Immunol. 165: 1082-1092 [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. JEM 192: 63-76 [Abstract] [Full Text]  
• Kumaraguru, U., Rouse, B. T. (2000). Application of the Intracellular Gamma Interferon Assay To Recalculate the Potency of CD8+ T-Cell Responses to Herpes Simplex Virus. J. Virol. 74: 5709-5711 [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]  
• Haanen, J. B.A.G., Wolkers, M. C., Kruisbeek, A. M., Schumacher, T. N.M. (1999). Selective Expansion of Cross-reactive CD8+ Memory T Cells by Viral Variants. JEM 190: 1319-1328 [Abstract] [Full Text]  
• Ogg, G. S., Kostense, S., Klein, M. R., Jurriaans, S., Hamann, D., McMichael, A. J., Miedema, F. (1999). Longitudinal Phenotypic Analysis of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes: Correlation with Disease Progression. J. Virol. 73: 9153-9160 [Abstract] [Full Text]  
• Whelan, J. A., Dunbar, P. R., Price, D. A., Purbhoo, M. A., Lechner, F., Ogg, G. S., Griffiths, G., Phillips, R. E., Cerundolo, V., Sewell, A. K. (1999). Specificity of CTL Interactions with Peptide-MHC Class I Tetrameric Complexes Is Temperature Dependent. J. Immunol. 163: 4342-4348 [Abstract] [Full Text]  
• Kolowos, W., Schmitt, M., Herrman, M., Harrer, E., Low, P., Kalden, J. R., Harrer, T. (1999). Biased TCR Repertoire in HIV-1-Infected Patients Due to Clonal Expansion of HIV-1-Reverse Transcriptase-Specific CTL Clones. J. Immunol. 162: 7525-7533 [Abstract] [Full Text]  
• Weekes, M. P., Carmichael, A. J., Wills, M. R., Mynard, K., Sissons, J. G. P. (1999). Human CD28-CD8+ T Cells Contain Greatly Expanded Functional Virus-Specific Memory CTL Clones. J. Immunol. 162: 7569-7577 [Abstract] [Full Text]  
• Molldrem, J. J., Lee, P. P., Wang, C., Champlin, R. E., Davis, M. M. (1999). A PR1-Human Leukocyte Antigen-A2 Tetramer Can Be Used to Isolate Low-Frequency Cytotoxic T Lymphocytes from Healthy Donors That Selectively Lyse Chronic Myelogenous Leukemia. Cancer Res. 59: 2675-2681 [Abstract] [Full Text]  
• Allen, R. L., O'Callaghan, C. A., McMichael, A. J., Bowness, P. (1999). Cutting Edge: HLA-B27 Can Form a Novel {beta}2-Microglobulin-Free Heavy Chain Homodimer Structure. J. Immunol. 162: 5045-5048 [Abstract] [Full Text]  
• Allan, D. S.J., Colonna, M., Lanier, L. L., Churakova, T. D., Abrams, J. S., Ellis, S. A., McMichael, A. J., Braud, V. M. (1999). Tetrameric Complexes of Human Histocompatibility Leukocyte Antigen (HLA)-G Bind to Peripheral Blood Myelomonocytic Cells. JEM 189: 1149-1156 [Abstract] [Full Text]  
• Weekes, M. P., Wills, M. R., Mynard, K., Carmichael, A. J., Sissons, J. G. P. (1999). The Memory Cytotoxic T-Lymphocyte (CTL) Response to Human Cytomegalovirus Infection Contains Individual Peptide-Specific CTL Clones That Have Undergone Extensive Expansion In Vivo. J. Virol. 73: 2099-2108 [Abstract] [Full Text]  
• Mongkolsapaya, J., Jaye, A., Callan, M. F. C., Magnusen, A. F., McMichael, A. J., Whittle, H. C. (1999). Antigen-Specific Expansion of Cytotoxic T Lymphocytes in Acute Measles Virus Infection. J. Virol. 73: 67-71 [Abstract] [Full Text]  
• Ogg, G. S., Jin, X., Bonhoeffer, S., Moss, P., Nowak, M. A., Monard, S., Segal, J. P., Cao, Y., Rowland-Jones, S. L., Hurley, A., Markowitz, M., Ho, D. D., McMichael, A. J., Nixon, D. F. (1999). Decay Kinetics of Human Immunodeficiency Virus-Specific Effector Cytotoxic T Lymphocytes after Combination Antiretroviral Therapy. J. Virol. 73: 797-800 [Abstract] [Full Text]  
• Coulie, P. G., Karanikas, V., Colau, D., Lurquin, C., Landry, C., Marchand, M., Dorval, T., Brichard, V., Boon, T. (2001). A monoclonal cytolytic T-lymphocyte response observed in a melanoma patient vaccinated with a tumor-specific antigenic peptide encoded by gene MAGE-3. Proc. Natl. Acad. Sci. USA 98: 10290-10295 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS