Skip to main content

Advertisement

SpringerLink
Log in

Study of the T cell receptor repertoire in viral immunodeficiency disease

  • Published:
Springer Seminars in Immunopathology Aims and scope Submit manuscript

Conclusion

In recent years, descriptive studies of the T cell repertoire have contributed in several ways to our understanding of immunodeficiency disease. In human AIDS, it was shown that, overall, TCR repertoire perturbations of various magnitude were taking place throughout the course of disease in both the CD4+ and CD8+ T cell subsets. Available evidence suggests that the repertoire is remarkably stable within a given individual in absence of serious pathological conditions, even across long periods of time (Ciurli et al., unpublished). The fact that patients with AIDS present with TCR repertoire perturbations, even throughout the so-called clinically silent phase of the disease, testifies to the extent of immune destruction that is taking place covertly within the peripheral lymphoid tissues. Since preferential deletions of CD4+ T cells expressing specific Vβ subsets are not consistently seen, and since no HIV protein has so far fulfilled all the classical characteristics of SAgs, one must argue that there is so far little support for the proposal that HIV encodes a conventional SAg. Preferential replication of HIV-1 in Vβ12+ cells seemed to provide both specificity and functional purpose for such an HIV-encoded SAg. However, it now seems that this superantigenic activity is in fact associated more closely with CMV infection. The fact that HIV uses SAg activity supplied in trans by a co-infecting pathogen is another good example of how lentiviruses and herpesviruses mutually profit from each other's functions to further their individual replicative needs. Whether this Vβ12 reservoir is in fact pathologically relevant still remains to be addressed.

Whereas repertoire studies have failed to reveal the presence of a virally encoded SAg in MAIDS virus infection, they have nevertheless suggested the possibility that indirect, perhaps integration-mediated para-oncogenic events, could be involved in the enhanced expression of endogenousmtv genes, and the observed in vitro Vβ-specific expansions. The importance of indirect SAg expression to the pathogenesis of MAIDS, perhaps in terms of expanding the viral reservoir, is so far unclear.

Finally, TCR repertoire studies have also revealed the existence of high-level Vβ-specific expansions, occurring in some patients during the acute phase of HIV infection. All available evidence suggests that these expansions are part of the early cell-mediated immune response to HIV antigens, and are most probably involved in the clearance of the initial viremic episode. These findings are well supported by studies of SIV infection in rhesus macaques. Idiotypic differences in the Vβ expansion patterns, which so far appear to be correlated with disease prognosis, may reflect the differential ability of an individual's TCR repertoire to recognize various HIV cytotoxic epitopes, and/or the relative restriction in the presentation of these peptides by given HLA haplotypes. In other words, a restricted, high-affinity response could be easily counteracted by the virus: selective mutations in cytotoxic epitopes have been documented that abrogate recognition by circulating cytotoxic T cell clones, and that eventually drift far enough from the initial epitope so as to escape presentation by the original class I allele. At the same time, high-level expansion of a T cell clone bearing a high-affinity receptor in the presence of a high viral load could make these T cell clones susceptible to peripheral deletion via high-dose tolerance and clonal exhaustion mechanisms [87]. Several rounds of such a routine would leave the host functionally defenseless with respect to cell-mediated immunity. Through expanded TCR repertoire analysis, we trust that this phenomenon will be revealed in other acute lymphotropic viral infections such as infectious mononucleosis. This type of acute Vβ-specific expansions of T cells expressing activated cytotoxic activity might be a more generalized mechanism of host antiviral response than has been previously thought.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Toyonaga B, Yoshikai Y, Vadasz V, Chin B, Mak TW (1985) Organization and sequences of the diversity, joining, and constant region genes of the human T-cell receptor beta chain. Proc Natl Acad Sci USA 82:8624

    Google Scholar 

  2. Toyonaga B, Mak TW (1987) Genes of the T cell antigen receptor in normal and malignant T cells. Annu Rev immunol 5:585

    Google Scholar 

  3. Wilson RK, Lai E, Concannon P, Barth RK, Good LE (1988) Structure, organization and polymorphism of murine and human T cell receptorα andβ gene families. Immunol Rev 101:149

    Google Scholar 

  4. Wei S, Charmley P, Robison MA, Concannon P (1994) The extent of the human germ-line T-cell receptor Vβ gene segment repertoire. Immunogenetics 40:27

    Google Scholar 

  5. Panzara MA, Gussoni E, Steinman L, Oksenberg JR (1991) Analysis of the T cell repertoire using PCR and specific oligonucleotide primers. BioTechniques 12:728

    Google Scholar 

  6. Hall BL, Finn OJ (1992) PCR-based analysis of the T cell receptor Vβ multigene family: experimental parameters affecting its validity. BioTechniques 13:248

    Google Scholar 

  7. Labrecque N, McGrath H, Subramanyam M, Huber BT, Sékaly RP (1993) Human T cells respond to mouse mammary tumor virus-encoded superantigen: Vβ restriction and conserved evolutionary features. J Exp Med 177:1735

    Google Scholar 

  8. Rebai N, Pantaleo G, Demarest JF, Ciurli C, Soudeyns H, Adelsberger JW, Vaccarezza M, Walker RE, Sékaly RP, Fauci AS (1994) Analysis of the T-cell receptorβ-chain variable-region (Vβ) repertoire in monozygotic twins discordant for human immunodeficiency virus: evidence for perturbations of specific Vβ segments in CD4+ T cells of the virus-positive twins. Proc Natl Acad Sci USA 91:1529

    Google Scholar 

  9. Choi Y, Kotzin B, Herron L, Callahan J, Marrack P, Kappler J (1989) Interaction ofStaphlococcus aureus toxin superantigens with human T cells. Proc Natl Acad Sci USA 86:8941

    Google Scholar 

  10. Wang X, Ohmen JD, Uyemura K, Rea TH, Kronenberg M, Modlin RL (1993) Selection of T lymphocytes bearing limited T-cell receptorβ chains in response to a human pathogen. Proc Natl Acad Sci USA 90:188

    Google Scholar 

  11. Akolkar P, Gulwani-Akolkar NB, Pergolizzi R, Bigler RD, Silver J (1993) Influence of HLA genes on T cell receptor V segment frequencies and expression levels in peripheral blood lymphocytes. J Immunol 150:2761

    Google Scholar 

  12. Gulwani-Akolkar B, Posnett DN, Janson CH, Grunwald J, Wigzell H, Akolkar P, Gregersen PK, Silver J (1991) T cell receptor V-segment frequencies in peripheral blood T cells correlate with human leukocyte antigen type. J Exp Med 174:1139

    Google Scholar 

  13. Kozak C, Peters G, Pauley R, Morris V, Michalides R, Dudley J, Green M, Davisson M, Prakash O, Vaidya A (1987) A standardized nomenclature for endogenous mouse mammary tumor viruses. J Virol 61:1651

    Google Scholar 

  14. Jouvin-Marche E, Cazenave PA, Voegtle D, Marche PN (1992) V beta 17 T-cell deletion by endogenous mammary tumor virus in wild-type-derived mouse strain. Proc Natl Acad Sci USA 89:3232

    Google Scholar 

  15. Golovkina UA, Chervonsky A, Dudley JP, Ross SR (1992) Transgenic mouse mammary tumor virus superantigen expression prevents viral infection. Cell 69:637

    Google Scholar 

  16. Held W, Waanders GA, Shakhov AN, Scarpellino L, Ach-Orbea H, MacDonald HR (1993) Superantigeninduced immune stimulation amplifies mouse mammary tumor virus infection and allows virus transmission. Cell 74:529

    Google Scholar 

  17. Lafon M, Lafage M, Martinez-Arends A, Ramirez R, Vuillier F, Charron D, Lotteau V, Scott-Algara D (1992) Evidence for a viral superantigen in humans. Nature 358:507

    Google Scholar 

  18. Hanto DW, Frizzera KJ, Gajl-Peczalska, Simmons RL (1985) Epstein-Barr virus, immunodeficiency and B cell lymphoproliferation. Transplantation 39:461

    Google Scholar 

  19. Fauci AS (1988) The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science 239:617

    Google Scholar 

  20. Pantaleo G, Graziosi C, Fauci AS (1993) The immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 328:327

    Google Scholar 

  21. Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, Pezeshkpour GH, Yungbluth M, Janotta F, Aksamit A, Martin MA and Fauci AS (1986) Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233:1089

    Google Scholar 

  22. Gabuzda DH, Ho DD, Monte SM de la, Hissch MS, Rota TR, Sobel RA (1986) Immunohistochemical identification of HTLV-III antigen in brains of patients with AIDS. Ann Neurol 20:289

    Google Scholar 

  23. Pantaleo G, Fauci AS (1995) New concepts in the immunopathogenesis of HIV infection. Ann Rev Immunol 13:487

    Google Scholar 

  24. Clark SJ, Shaw GM (1993) The acute retroviral syndrome and the pathogenesis of HIV-1 infection. Semin Immunol 5:149

    Google Scholar 

  25. Klatzmann D, Barré-Sinoussi F, Nugeyre MT, Dauguet C, Vilmer E, Griscelli C, Brun-Vézinet F, Rouzioux C, Gluckman JC, Chermann J-C, Montagnier L (1984) Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science 225:59

    Google Scholar 

  26. Maddon PJ, Dalgleish AG, McDougal JS, Clapham PR, Weiss RA, Axel R (1986) The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 47:333

    Google Scholar 

  27. Chen ZW, Kou ZC, Lekutis C, Shen L, Zhou D, Halloran M, Li J, Sodroski J, Lee-Parritz D, Letvin NI (1995) T cell receptor Vβ repertoire in an acute infection of Rhesus monkeys with simian immunodeficiency viruses and a chimeric simian-human immunodeficiency virus. J Exp Med 182:21

    Google Scholar 

  28. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M (1995) Rapide turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123

    Google Scholar 

  29. Garry RF (1989) Potential mechanisms for the cythopathic properties of HIV. AIDS 3:683

    Google Scholar 

  30. Sodroski J, Goh WC, Rosen C, Campbell K, Haseltine WA (1986) Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. Nature 322:470

    Google Scholar 

  31. Siliciano RF, Lawton T, Knall, Karr RW, Berman P, Gregory T, Reinherz EL (1988) Analysis of host-virus interactions in AIDS with anti-gp120 T cell clones: effect of HIV sequence variation and a mechanism for CD4+ cell depletion. Cell 54:561

    Google Scholar 

  32. Garcia JV, Miller AD (1991) Serine phosphorylation-independent downregulation of cell-surface CD4 bynef. Nature 350:508

    Google Scholar 

  33. Laurent-Crawford AG, Krust B, Muller S (1991) The cytopathic effect of HIV is associated with apoptosis. Virology 185:829

    Google Scholar 

  34. Banda NK, Bernier J, Kurahara DK, Kurie R, Haigwood N, Sékaly RP, Finkel TH (1992) Cross-linking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis. J Exp Med 176:1099

    Google Scholar 

  35. Groux H, Torpier G, Monte D, Mouton Y, Capron A, Ameisen JC (1992) Activation-induced death by apoptosis in CD4+T cells from human immunodeficiency virus-infected asymptomatic individuals. J Exp Med 175:331

    Google Scholar 

  36. Pope M, Betjes MG, Romani N, Hirmand H, Cameron PU, Hoffman L, Gezelter S, Sculer G, Steinman RM (1994) Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell 78:389

    Google Scholar 

  37. Janeway C (1991) Mls: makes a little sense. News and views. Nature 349:459

    Google Scholar 

  38. Imberti L, Sottini A, Bettinardi A, Puoti M, Primi D (1991) Selective depletion in HIV infection of T cells that bear specific T cell receptor Vβ sequences. Science 254:860

    Google Scholar 

  39. Dalgleish AG, Wilson S, Gompels M, Ludlam C, Gazzard B, Coates AM, Habeshaw J (1992) T-cell receptor variable gene products and early HIV-1 infection. Lancet 339:824

    Google Scholar 

  40. Soudeyns H, Rebai N, Pantaleo GP, Ciurli C, Boghossian T, Sékaly RP, Fauci A (1993) The T cell receptor Vβ repertoire in HIV-1 infection and disease. Semin Immunol 5:165

    Google Scholar 

  41. Hodara VL, Jeddi-Tehrani M, Grunewald J, Andersson R, Scarlatti G, Esin S, Holmberg V, Libonatti O, Wigzell H (1993) HIV infection leads to differential expression of T-cell receptor Vβ genes in CD4+ and CD8+ T cells. AIDS 7:633

    Google Scholar 

  42. Pantaleo G, Graziosi C, Demarest JF, Butini L, Montroni M, Fox CH, Orenstein JM, Kotler DP, Fauci AS (1993) HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature 362:355

    Google Scholar 

  43. Embretson J, Zupanic M, Ribas JL, Burke A, Racz P, Tenner-Racz K, Haase AT (1993) Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature 362:359

    Google Scholar 

  44. Soudeyns H, Routy JP, Sékaly RP (1994) Comparative analysis of the T cell receptor V-β repertoire in various lymphoid tissues from HIV-infected patients: evidence for an HIV-associated superantigen. Leukemia 8 [Suppl 1]:S95

    Google Scholar 

  45. Clark SJ, Saag MS, Decker WD, Campbell-Hill S, Roberson JL, Veldkamp PJ, Kappes JC, Hahn BH, Shaw GM (1991) High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. N Engl J Med 324:954

    Google Scholar 

  46. Graziosi C, Pantaleo G, Butini L, Demarest JF, Saag MS Shaw GM, Fauci AS (1993) Kinetics of HIV DNA and RNA synthesis during primary HIV-1 infection. Proc Natl Acad Sci USA 90:6505

    Google Scholar 

  47. Pantaleo G, Demarest JF, Soudeyns H, Graziosi C, Denis F, Adelsberger JW, Borrow P, Saag MS, Shaw GM, Sékaly RP, Fauci AS (1994) Major expansion of CD8+ T cells with a predominant Vβ usage during the primary immune response to HIV. Nature 370:463

    Google Scholar 

  48. Silverstri G, Soudeyns H, Lapointe N, Samson J, Denis F, Sékaly RP (1995) T cell receptor specific Vβ-specific expansions in children from HIV-infected mothers. AIDS (in press)

  49. Posnett DN, Kabak S, Hodtsev AS, Goldberg EA, Asch A (1993) T-cell antigen receptor V-β subsets are not preferentially deleted in AIDS. AIDS 7:625

    Google Scholar 

  50. Boyer V, Smith LR, Ferre F, Pezzoli P, Trauger RJ, Jensen FC, Carlo DJ (1993) T cell receptor Vβ repertoire in HIV-infected individuals: lack of evidence for selective Vβ deletion. Clin Exp Immunol 92:437

    Google Scholar 

  51. Nisini R, Aiuti A, Matricardi PM, Fattorossi A, Ferlini C, Biselli R, Mezzaroma I, Pinter E, D'Amelio R (1994) Lack of evidence for a superantigen in lymphocytes from HIV-discordant monozygotic twins. AIDS 8:443

    Google Scholar 

  52. Trono D (1995) HIV accessory proteins: leading roles for the supporting cast. Cell 82:189

    Google Scholar 

  53. Torres BA, Johnson HM (1994) Identification of an HIV-1 Nef peptide that binds to HLA class II antigens. Biochem Biophys Res Commun 200:1059

    Google Scholar 

  54. Laurence J, Hodtsev AS, Posnett DN (1992) Superantigen implicated in dependence of HIV-1 replication in T cells on TCR Vβ expression. Nature 358:255

    Google Scholar 

  55. Dobrescu D, Kabak S, Mehta K, Suh CH, Asch A, Cameron PU, Hodtsev AS, Posnett DN (1995) Human immunodeficiency virus 1 reservoir in CD4+ T cells is restricted to certain Vβ subsets. Proc Natl Acad Sci USA 92:5563

    Google Scholar 

  56. Ignatowicz L, Kappler J, Marrack P (1992) The effects of chronic infection with a superantigenproducing virus. J Exp Med 175:917

    Google Scholar 

  57. McCormack JE, Callahan JE, Kappler J, Marrack PC (1993) Profound deletion of mature T cells in vivo by chronic exposure to exogenous superantigen. J Immunol 150:3785

    Google Scholar 

  58. Dadaglio G, Garcia S, Montagnier L, Gougeon M-L (1994) Selective anergy of Vβ8+ T cells in human immunodeficiency virus-infected individuals. J Exp Med 179:413

    Google Scholar 

  59. Dobrescu D, Ursea B, Pope M, Asch AS, Posnett DN (1995) Enhanced HIV-1 replication in Vβ12 T cells due to human cytomegalovirus in monocytes: evidence for a putative herpesvirus superantigen. Cell 82:753

    Google Scholar 

  60. Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M (1986) The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233:215

    Google Scholar 

  61. Alter HJ, Eichberg JW, Masur H, Saxinger WC, Gallo R, Macher AM, Lane HC, Fauci AS (1984) Transmission of HTLV-III infection from human plasma to chimpanzees: an animal model for AIDS. Science 226:549

    Google Scholar 

  62. Fultz, PN, McClure HM, Swenson RB, McGrath CR, Brodie A, Getchell JP, Jensen FC, Anderson DC, Broderson JR, Francis DP (1986) Persistent infection of chimpanzees with human T-lymphotropic virus type III/lymphadenopathy-associated virus: a potential model for acquired immunodeficiency syndrome. J Virol 58:116

    Google Scholar 

  63. Desrosiers RC (1988) Simian immunodeficiency viruses. Annu Rev Microbiol 42:607

    Google Scholar 

  64. Daniel MD, Letvin NL, King NW, Kannagi M, Sehgal PK, Hunt RD, Kanki PJ, Essex M, Desrosiers RC (1985) Isolation of T-cell tropic HTLV-III-like retrovirus from macaques. Science 228:1201

    Google Scholar 

  65. Meyers G, Rabson AB, Berzofsky JA, Smith FT and Wong-Staals, (eds) (1990). Human retroviruses and AIDS: acompilation and analysis of nucleic acid and amino acid sequences. Los Alamos National Laboratory, New Mexico

    Google Scholar 

  66. Desrosiers RC (1990) The simian immunodeficiency viruses. Annu Rev Immunol 8:557

    Google Scholar 

  67. Beneviste RE, Morton WR, Clark EA, Tsai CC, Ochs HD, Ward JM, Kuller L, Knott WB, Hill RW, Gale MJ, Thouless ME (1988) Inoculation of baboons and macaques with simian immunodeficiency virus/Mne, a primate lentivirus closely related to human immunodeficiency virus type 2. J Virol 62:2091

    Google Scholar 

  68. Letvin NL, Daniel MD, Sehgal PK, Desrosiers RC, Hunt RD, Waldron LM, Mackey JJ, Schmidt DK, Chalifoux LV, King NW (1985) Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III. Science 230:71

    Google Scholar 

  69. Murphey-Corb M, Martin LN, Rangan SRS, Baskin GB, Gormus BJ, Wolf RH, Andes WA, West M, Montelaro RC (1986) Isolation of an HTLV-III-related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys. Nature 321:435

    Google Scholar 

  70. Chen ZW, Kou Z-C, Shen L, Reimann KA, Letvin NM (1993) Conserved T-cell receptor repertoire in simian immunodeficiency virus-infected Rhesus monkeys. J Immunol 151:2177

    Google Scholar 

  71. Fultz PN, McClure HM, Anderson DC, Switzer WM (1989) Identification and biological characterization of an acutely lethal variant of simian immunodeficiency virus from sooty mangabeys (SIV/SMM). AIDS Res Hum Retroviruses 5:397

    Google Scholar 

  72. Lewis MG, Zack PM, Elkins WR, Jahrling PB (1992) Infection of Rhesus and Cynomolgus macaclues with a rapidly fatal SIV (SIV SMM/PBj) isolate from sooty mangabeys. AIDS Res Hum Retrovir 8:1631

    Google Scholar 

  73. Novembre FJ, Johnson PR, Lewis MG, Anderson DC, Klumpp S, McClure HM, Hirsch VM (1993) Multiple viral determinants contribute to pathogenicity of the acutely lethal simian immunodeficiency virus SIVsmmPBj variant. J Virol 67:2466

    Google Scholar 

  74. Dewhurst S, Embretson JE, Anderson DC, Mullins JI, Fultz PN (1990) Sequence analysis and acute pathogenicity of molecularly cloned SIVsmm-PBj14. Nature 345:636

    Google Scholar 

  75. Du Z, Lang SM, Sasseville VG, Lackner AA, Ilyinskii PO, Daniel MD, Jung JU, Desrosiers RC (1995) Identification of a nef allele that causes lymphocyte activation and acute disease in macaque monkeys. Cell 82:665

    Google Scholar 

  76. Legrand E, Daculsi R, Duplan JF (1981) Characteristics of the cell populations involved in extra-thymic lymphosarcoma induced in C57BL/6 mice by RadLV-Rs. Leuk Res 5:223

    Google Scholar 

  77. Aziz DC, Hanna Z, Jolicoeur P (1989) Severe immunodeficiency disease induced by a defective murine leukaemia virus. Nature 338:505

    Google Scholar 

  78. Hartley JW, Fredrickson TN, Yetter RA, Makino M, Morse HC III (1989) Retrovirus-induced murine acquired immunodeficiency syndrome: natural history of infection and differing susceptibility of inbred mouse strains. J Virol 63:1223

    Google Scholar 

  79. Morse HC III, Chattopadhyay SK, Makino M, Fredrickson TN, Hügin AW, Hartley JW (1992) Retrovirus-induced immunodeficiency in the mouse: MAIDS as a model for AIDS. AIDS 6:607

    Google Scholar 

  80. Kubo Y, Nakagawa Y, Kakimi K, Matsui H, Iwashiro M, Kuribayashi K, Masuda T, Hiai H, Hirama T, Yanagawa SI, Ishimoto A (1992) Presence of transplantable T-lymphoid cells in C57BL/6 mice infected with murine AIDS virus. J Virol 66:5691

    Google Scholar 

  81. Huang M, Simard C, Kay DG, Jolicoeur P (1991) The majority of cells infected with the defective murine AIDS virus belong to the B cell lineage. J Virol 65:6562

    Google Scholar 

  82. Simard C, Jolicoeur P (1991) The effect of anti-neoplastic drugs on murine acquired immunodeficiency syndrome. Science 251:305

    Google Scholar 

  83. Huang M, Hanna Z, Jolicoeur P (1995) Mutational analysis of the murine AIDS-defective viral genome reveals a high reversion rate in vivo and a requirement for an intact pr60gag protein for efficient induction of disease. J Virol 69:60

    Google Scholar 

  84. Hügin AW, Vacchio MS, Morse III HC (1991) A virus-encoded superantigen in a retrovirus-induced immunodeficiency syndrome of mice. Science 252:424

    Google Scholar 

  85. Selvey LA, Morse HC III, Granger LG, Hodes RJ (1993) Preferential expansion and activation of Vβ5+ CD4+ T cells in murine acquired immunodeficiency syndrome. J Immunol 515:1712

    Google Scholar 

  86. Huang M, Takac M, Kozac CA, Jolicoeur P (1995) The murine AIDS defective provirus acts as an insertional mutagen in its infected target B cells. J Virol 69:4069

    Google Scholar 

  87. Moskophidis D, Lechner F, Pircher H, Zinkernagel RM (1993) Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells. Nature 362:758

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, H2W 1R7, Montréal, Québec, Canada

    Cristina Ciurli, Rafick-Pierre Sékaly & Hugo Soudeyns

  2. Département de Microbiologie et d'Immunologie, Université de Montréal, Montréal, Québec, Canada

    Cristina Ciurli & Rafick-Pierre Sékaly

  3. Département of Microbiology and Immunology, McGill University, Montréal, Québec, Canada

    Rafick-Pierre Sékaly & Hugo Soudeyns

Authors
  1. Cristina Ciurli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rafick-Pierre Sékaly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hugo Soudeyns
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ciurli, C., Sékaly, RP. & Soudeyns, H. Study of the T cell receptor repertoire in viral immunodeficiency disease. Springer Semin Immunopathol 17, 319–332 (1996). https://doi.org/10.1007/BF01795132

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01795132

Keywords

Search

Navigation