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CD8+ T cell efficacy in vaccination and disease

Abstract

Much effort has been devoted to the design of vaccines that induce adaptive cellular immunity, in particular CD8+ T cells, which have a central role in the host response to viral infections and cancers. To date, however, the development of effective T cell vaccines remains elusive. This is due, in part, to the lack of clearly defined correlates of protection and the inherent difficulties that hinder full characterization of the determinants of successful T cell immunity in humans. Recent data from the disparate fields of infectious disease and tumor immunology have converged, with an emphasis on the functional attributes of individual antigen-specific T cell clonotypes, to provide a better understanding of CD8+ T cell efficacy. This new knowledge paves the way to the design of more effective T cell vaccines and highlights the importance of comprehensive immunomonitoring.

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Figure 1: The relationship between CD8+ T cell attributes and immune efficacy.
Figure 2: Control of viral replication by CD8+ T cells and HIV disease progression.

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References

  1. Mattapallil, J.J. et al. Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge. J. Exp. Med. 203, 1533–1541 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Migueles, S.A. et al. HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long-term nonprogressors. Proc. Natl. Acad. Sci. USA 97, 2709–2714 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Betts, M.R. et al. Analysis of total human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T cell responses: relationship to viral load in untreated HIV infection. J. Virol. 75, 11983–11991 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Lee, P.P. et al. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat. Med. 5, 677–685 (1999).

    CAS  PubMed  Google Scholar 

  5. Dunbar, P.R. et al. A shift in the phenotype of melan-A–specific CTL identifies melanoma patients with an active tumor-specific immune response. J. Immunol. 165, 6644–6652 (2000).

    CAS  PubMed  Google Scholar 

  6. Appay, V. et al. HIV-specific CD8+ T cells produce antiviral cytokines but are impaired in cytolytic function. J. Exp. Med. 192, 63–75 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Champagne, P. et al. Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature 410, 106–111 (2001).

    CAS  PubMed  Google Scholar 

  8. Speiser, D.E. et al. In vivo activation of melanoma-specific CD8+ T cells by endogenous tumor antigen and peptide vaccines. A comparison to virus-specific T cells. Eur. J. Immunol. 32, 731–741 (2002).

    CAS  PubMed  Google Scholar 

  9. Mortarini, R. et al. Lack of terminally differentiated tumor-specific CD8+ T cells at tumor site in spite of antitumor immunity to self antigens in human metastatic melanoma. Cancer Res. 63, 2535–2545 (2003).

    CAS  PubMed  Google Scholar 

  10. Appay, V. et al. Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat. Med. 8, 379–385 (2002).

    CAS  PubMed  Google Scholar 

  11. Betts, M.R. et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107, 4781–4789 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Wherry, E.J. et al. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat. Immunol. 4, 225–234 (2003).

    CAS  PubMed  Google Scholar 

  13. Gattinoni, L. et al. Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J. Clin. Invest. 115, 1616–1626 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Sacre, K. et al. Repertoire, diversity, and differentiation of specific CD8 T cells are associated with immune protection against human cytomegalovirus disease. J. Exp. Med. 201, 1999–2010 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Berger, C. et al. Adoptive transfer of effector CD8 T cells derived from central memory cells establishes persistent T cell memory in primates. J. Clin. Invest. 118, 294–305 (2008).

    CAS  PubMed  Google Scholar 

  16. Day, C.L. et al. PD-1 expression on HIV-specific T cells is associated with T cell exhaustion and disease progression. Nature 443, 350–354 (2006).

    CAS  PubMed  Google Scholar 

  17. Trautmann, L. et al. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat. Med. 12, 1198–1202 (2006).

    CAS  PubMed  Google Scholar 

  18. Petrovas, C. et al. PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. J. Exp. Med. 203, 2281–2292 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Sauce, D. et al. PD-1 expression on human CD8 T cells depends on both state of differentiation and activation status. AIDS 21, 2005–2013 (2007).

    CAS  PubMed  Google Scholar 

  20. Migueles, S.A. et al. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat. Immunol. 3, 1061–1068 (2002).

    CAS  PubMed  Google Scholar 

  21. Zhou, J. et al. Telomere length of transferred lymphocytes correlates with in vivo persistence and tumor regression in melanoma patients receiving cell transfer therapy. J. Immunol. 175, 7046–7052 (2005).

    CAS  PubMed  Google Scholar 

  22. Harari, A., Petitpierre, S., Vallelian, F. & Pantaleo, G. Skewed representation of functionally distinct populations of virus-specific CD4 T cells in HIV-1–infected subjects with progressive disease: changes after antiretroviral therapy. Blood 103, 966–972 (2004).

    CAS  PubMed  Google Scholar 

  23. Almeida, J.R. et al. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J. Exp. Med. 204, 2473–2485 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Beveridge, N.E. et al. Immunisation with BCG and recombinant MVA85A induces long-lasting, polyfunctional Mycobacterium tuberculosis–specific CD4+ memory T lymphocyte populations. Eur. J. Immunol. 37, 3089–3100 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Darrah, P.A. et al. Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat. Med. 13, 843–850 (2007).

    CAS  PubMed  Google Scholar 

  26. Precopio, M.L. et al. Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8+ T cell responses. J. Exp. Med. 204, 1405–1416 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Derby, M., Alexander-Miller, M., Tse, R. & Berzofsky, J. High-avidity CTL exploit two complementary mechanisms to provide better protection against viral infection than low-avidity CTL. J. Immunol. 166, 1690–1697 (2001).

    CAS  PubMed  Google Scholar 

  28. Bennett, M.S., Ng, H.L., Dagarag, M., Ali, A. & Yang, O.O. Epitope-dependent avidity thresholds for cytotoxic T-lymphocyte clearance of virus-infected cells. J. Virol. 81, 4973–4980 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Speiser, D.E., Kyburz, D., Stubi, U., Hengartner, H. & Zinkernagel, R.M. Discrepancy between in vitro measurable and in vivo virus-neutralizing cytotoxic T cell reactivities. Low T cell receptor specificity and avidity sufficient for in vitro proliferation or cytotoxicity to peptide-coated target cells but not for in vivo protection. J. Immunol. 149, 972–980 (1992).

    CAS  PubMed  Google Scholar 

  30. Alexander-Miller, M.A., Leggatt, G.R. & Berzofsky, J.A. Selective expansion of high- or low-avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy. Proc. Natl. Acad. Sci. USA 93, 4102–4107 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Messaoudi, I., Guevara Patino, J.A., Dyall, R., LeMaoult, J. & Nikolich-Zugich, J. Direct link between MHC polymorphism, T cell avidity and diversity in immune defense. Science 298, 1797–1800 (2002).

    CAS  PubMed  Google Scholar 

  32. Yee, C., Savage, P.A., Lee, P.P., Davis, M.M. & Greenberg, P.D. Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide-MHC tetramers. J. Immunol. 162, 2227–2234 (1999).

    CAS  PubMed  Google Scholar 

  33. Zeh, H.J. III, Perry-Lalley, D., Dudley, M.E., Rosenberg, S.A. & Yang, J.C. High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy. J. Immunol. 162, 989–994 (1999).

    CAS  PubMed  Google Scholar 

  34. Dutoit, V. et al. Heterogeneous T cell response to MAGE-A10254–262: high avidity–specific cytolytic T lymphocytes show superior antitumor activity. Cancer Res. 61, 5850–5856 (2001).

    CAS  PubMed  Google Scholar 

  35. Belyakov, I.M. et al. Impact of vaccine-induced mucosal high-avidity CD8+ CTLs in delay of AIDS viral dissemination from mucosa. Blood 107, 3258–3264 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. O'Connor, D.H. et al. Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection. Nat. Med. 8, 493–499 (2002).

    CAS  PubMed  Google Scholar 

  37. Saez-Cirion, A. et al. HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc. Natl. Acad. Sci. USA 104, 6776–6781 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Cawthon, A.G., Lu, H. & Alexander-Miller, M.A. Peptide requirement for CTL activation reflects the sensitivity to CD3 engagement: correlation with CD8αβ versus CD8αα expression. J. Immunol. 167, 2577–2584 (2001).

    CAS  PubMed  Google Scholar 

  39. Schamel, W.W. et al. Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide range of response. J. Exp. Med. 202, 493–503 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Park, J.H. et al. 'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR. Nat. Immunol. 8, 1049–1059 (2007).

    CAS  PubMed  Google Scholar 

  41. Viola, A. & Lanzavecchia, A. T cell activation determined by T cell receptor number and tunable thresholds. Science 273, 104–106 (1996).

    CAS  PubMed  Google Scholar 

  42. Valitutti, S., Muller, S., Dessing, M. & Lanzavecchia, A. Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy. J. Exp. Med. 183, 1917–1921 (1996).

    CAS  PubMed  Google Scholar 

  43. Price, D.A. et al. Antigen-specific release of β-chemokines by anti–HIV-1 cytotoxic T lymphocytes. Curr. Biol. 8, 355–358 (1998).

    CAS  PubMed  Google Scholar 

  44. Betts, M.R. et al. The functional profile of primary human antiviral CD8+ T cell effector activity is dictated by cognate peptide concentration. J. Immunol. 172, 6407–6417 (2004).

    CAS  PubMed  Google Scholar 

  45. La Gruta, N.L., Turner, S.J. & Doherty, P.C. Hierarchies in cytokine expression profiles for acute and resolving influenza virus–specific CD8+ T cell responses: correlation of cytokine profile and TCR avidity. J. Immunol. 172, 5553–5560 (2004).

    CAS  PubMed  Google Scholar 

  46. Seder, R.A., Darrah, P.A. & Roederer, M. T cell quality in memory and protection: implications for vaccine design. Nat. Rev. Immunol. 8, 247–258 (2008).

    CAS  PubMed  Google Scholar 

  47. Huse, M. et al. Spatial and temporal dynamics of T cell receptor signaling with a photoactivatable agonist. Immunity 27, 76–88 (2007).

    CAS  PubMed  Google Scholar 

  48. Dzutsev, A.H., Belyakov, I.M., Isakov, D.V., Margulies, D.H. & Berzofsky, J.A. Avidity of CD8 T cells sharpens immunodominance. Int. Immunol. 19, 497–507 (2007).

    CAS  PubMed  Google Scholar 

  49. Price, D.A. et al. Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses. J. Exp. Med. 202, 1349–1361 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Trautmann, L. et al. Selection of T cell clones expressing high-affinity public TCRs within human cytomegalovirus–specific CD8 T cell responses. J. Immunol. 175, 6123–6132 (2005).

    CAS  PubMed  Google Scholar 

  51. Bihl, F. et al. Impact of HLA-B alleles, epitope binding affinity, functional avidity, and viral coinfection on the immunodominance of virus-specific CTL responses. J. Immunol. 176, 4094–4101 (2006).

    CAS  PubMed  Google Scholar 

  52. Speiser, D.E. et al. A novel approach to characterize clonality and differentiation of human melanoma-specific T cell responses: spontaneous priming and efficient boosting by vaccination. J. Immunol. 177, 1338–1348 (2006).

    CAS  PubMed  Google Scholar 

  53. Effros, R.B. & Pawelec, G. Replicative senescence of T cells: does the Hayflick Limit lead to immune exhaustion? Immunol. Today 18, 450–454 (1997).

    CAS  PubMed  Google Scholar 

  54. Lichterfeld, M. et al. 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 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Vezys, V. et al. Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection. J. Exp. Med. 203, 2263–2269 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Davenport, M.P., Fazou, C., McMichael, A.J. & Callan, M.F. Clonal selection, clonal senescence, and clonal succession: the evolution of the T cell response to infection with a persistent virus. J. Immunol. 168, 3309–3317 (2002).

    CAS  PubMed  Google Scholar 

  57. Douek, D.C. et al. 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 (2002).

    CAS  PubMed  Google Scholar 

  58. Price, D.A. et al. T cell receptor recognition motifs govern immune escape patterns in acute SIV infection. Immunity 21, 793–803 (2004).

    CAS  PubMed  Google Scholar 

  59. Lichterfeld, M. et al. A viral CTL escape mutation leading to immunoglobulin-like transcript 4–mediated functional inhibition of myelomonocytic cells. J. Exp. Med. 204, 2813–2824 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Davenport, M.P., Price, D.A. & McMichael, A.J. The T cell repertoire in infection and vaccination: implications for control of persistent viruses. Curr. Opin. Immunol. 19, 294–300 (2007).

    CAS  PubMed  Google Scholar 

  61. Douek, D.C., Picker, L.J. & Koup, R.A. T cell dynamics in HIV-1 infection. Annu. Rev. Immunol. 21, 265–304 (2003).

    CAS  PubMed  Google Scholar 

  62. Douek, D.C. et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 396, 690–695 (1998).

    CAS  PubMed  Google Scholar 

  63. Dion, M.L. et al. HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation. Immunity 21, 757–768 (2004).

    CAS  PubMed  Google Scholar 

  64. Jenkins, M., Hanley, M.B., Moreno, M.B., Wieder, E. & McCune, J.M. Human immunodeficiency virus-1 infection interrupts thymopoiesis and multilineage hematopoiesis in vivo. Blood 91, 2672–2678 (1998).

    CAS  PubMed  Google Scholar 

  65. Picker, L.J. et al. Insufficient production and tissue delivery of CD4+ memory T cells in rapidly progressive simian immunodeficiency virus infection. J. Exp. Med. 200, 1299–1314 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Letvin, N.L. et al. Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys. Science 312, 1530–1533 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Dudley, M.E. et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298, 850–854 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Johnson, L.A. et al. Gene transfer of tumor-reactive TCR confers both high avidity and tumor reactivity to nonreactive peripheral blood mononuclear cells and tumor-infiltrating lymphocytes. J. Immunol. 177, 6548–6559 (2006).

    CAS  PubMed  Google Scholar 

  69. Morgan, R.A. et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314, 126–129 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Walter, S. et al. Cutting edge: predetermined avidity of human CD8 T cells expanded on calibrated MHC–anti-CD28–coated microspheres. J. Immunol. 171, 4974–4978 (2003).

    CAS  PubMed  Google Scholar 

  71. Bullock, T.N., Mullins, D.W. & Engelhard, V.H. Antigen density presented by dendritic cells in vivo differentially affects the number and avidity of primary, memory, and recall CD8+ T cells. J. Immunol. 170, 1822–1829 (2003).

    CAS  PubMed  Google Scholar 

  72. Kroger, C.J. & Alexander-Miller, M.A. Cutting edge: CD8+ T cell clones possess the potential to differentiate into both high- and low-avidity effector cells. J. Immunol. 179, 748–751 (2007).

    CAS  PubMed  Google Scholar 

  73. Monsurro, V. et al. Quiescent phenotype of tumor-specific CD8+ T cells following immunization. Blood 104, 1970–1978 (2004).

    CAS  PubMed  Google Scholar 

  74. Narayan, S., Choyce, A., Fernando, G.J. & Leggatt, G.R. Secondary immunisation with high-dose heterologous peptide leads to CD8 T cell populations with reduced functional avidity. Eur. J. Immunol. 37, 406–415 (2007).

    CAS  PubMed  Google Scholar 

  75. Estcourt, M.J. et al. Prime-boost immunization generates a high frequency, high-avidity CD8+ cytotoxic T lymphocyte population. Int. Immunol. 14, 31–37 (2002).

    CAS  PubMed  Google Scholar 

  76. Oh, S. et al. Selective induction of high avidity CTL by altering the balance of signals from APC. J. Immunol. 170, 2523–2530 (2003).

    CAS  PubMed  Google Scholar 

  77. Hodge, J.W., Chakraborty, M., Kudo-Saito, C., Garnett, C.T. & Schlom, J. Multiple costimulatory modalities enhance CTL avidity. J. Immunol. 174, 5994–6004 (2005).

    CAS  PubMed  Google Scholar 

  78. Maher, J., Brentjens, R.J., Gunset, G., Riviere, I. & Sadelain, M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRζ /CD28 receptor. Nat. Biotechnol. 20, 70–75 (2002).

    CAS  PubMed  Google Scholar 

  79. Finney, H.M., Akbar, A.N. & Lawson, A.D. Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR ζ chain. J. Immunol. 172, 104–113 (2004).

    CAS  PubMed  Google Scholar 

  80. Sedlik, C. et al. In vivo induction of a high-avidity, high-frequency cytotoxic T-lymphocyte response is associated with antiviral protective immunity. J. Virol. 74, 5769–5775 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Castellino, F. & Germain, R.N. Cooperation between CD4+ and CD8+ T cells: when, where, and how. Annu. Rev. Immunol. 24, 519–540 (2006).

    CAS  PubMed  Google Scholar 

  82. Douek, D.C. et al. HIV preferentially infects HIV-specific CD4+ T cells. Nature 417, 95–98 (2002).

    CAS  PubMed  Google Scholar 

  83. Zhou, G., Drake, C.G. & Levitsky, H.I. Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood 107, 628–636 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Williams, M.A. & Bevan, M.J. Effector and memory CTL differentiation. Annu. Rev. Immunol. 25, 171–192 (2007).

    CAS  PubMed  Google Scholar 

  85. Speiser, D.E. et al. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA and CpG oligodeoxynucleotide 7909. J. Clin. Invest. 115, 739–746 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Wille-Reece, U. et al. Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates. J. Exp. Med. 203, 1249–1258 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Trumpfheller, C. et al. The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. Proc. Natl. Acad. Sci. USA 105, 2574–2579 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Belyakov, I.M., Isakov, D., Zhu, Q., Dzutsev, A. & Berzofsky, J.A. A novel functional CTL avidity/activity compartmentalization to the site of mucosal immunization contributes to protection of macaques against simian/human immunodeficiency viral depletion of mucosal CD4+ T cells. J. Immunol. 178, 7211–7221 (2007).

    CAS  PubMed  Google Scholar 

  89. Ranasinghe, C. et al. Mucosal HIV-1 pox virus prime-boost immunization induces high-avidity CD8+ T cells with regime-dependent cytokine/granzyme B profiles. J. Immunol. 178, 2370–2379 (2007).

    CAS  PubMed  Google Scholar 

  90. Critchfield, J.W. et al. Multifunctional human immunodeficiency virus (HIV) Gag-specific CD8+ T cell responses in rectal mucosa and peripheral blood mononuclear cells during chronic HIV type 1 infection. J. Virol. 81, 5460–5471 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Zhou, J., Dudley, M.E., Rosenberg, S.A. & Robbins, P.F. Selective growth, in vitro and in vivo, of individual T cell clones from tumor-infiltrating lymphocytes obtained from patients with melanoma. J. Immunol. 173, 7622–7629 (2004).

    CAS  PubMed  Google Scholar 

  92. Appay, V. et al. New generation vaccine induces effective melanoma-specific CD8+ T cells in the circulation but not in the tumor site. J. Immunol. 177, 1670–1678 (2006).

    CAS  PubMed  Google Scholar 

  93. Kiepiela, P. et al. CD8+ T cell responses to different HIV proteins have discordant associations with viral load. Nat. Med. 13, 46–53 (2007).

    CAS  PubMed  Google Scholar 

  94. Sacha, J.B. et al. Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression. J. Immunol. 178, 2746–2754 (2007).

    CAS  PubMed  Google Scholar 

  95. Friedrich, T.C. et al. Subdominant CD8+ T cell responses are involved in durable control of AIDS virus replication. J. Virol. 81, 3465–3476 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Appay, V. et al. Decreased specific CD8+ T cell cross-reactivity of antigen recognition following vaccination with Melan-A peptide. Eur. J. Immunol. 36, 1805–1814 (2006).

    CAS  PubMed  Google Scholar 

  97. Stuge, T.B. et al. Diversity and recognition efficiency of T cell responses to cancer. PLoS Med. 1, e28 (2004).

    PubMed  PubMed Central  Google Scholar 

  98. Speiser, D.E. et al. Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen. Proc. Natl. Acad. Sci. USA 105, 3849–3854 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Betts, M.R. et al. Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection. Proc. Natl. Acad. Sci. USA 102, 4512–4517 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Harari, A. et al. An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses. J. Exp. Med. 205, 63–77 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are very grateful to B. Autran and P. Romero for helpful discussions and critical reading of this manuscript. We apologize to the authors of many excellent and relevant studies that we have been unable to cite owing to formatting constraints. D.A.P. is a Medical Research Council (UK) Senior Clinical Fellow.

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Correspondence to Victor Appay.

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Appay, V., Douek, D. & Price, D. CD8+ T cell efficacy in vaccination and disease. Nat Med 14, 623–628 (2008). https://doi.org/10.1038/nm.f.1774

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