Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load

Journal of Virology

Volumn 77, Issue 3, 2003, Pages 2081-2092

  Addo, M M ^a   Yu, X G ^a   Rathod, A ^a   Cohen, D ^b   Eldridge, R L ^a   Strick, D ^a   Johnston, M N ^a   Corcoran, C ^a   Wurcel, A G ^a   Fitzpatrick, C A ^a   Feeney, M E ^a   Rodriguez, W R ^a   Basgoz, N ^a   Draenert, R ^a   Stone, David R ^c   Brander, C ^a   Goulder, P J R ^a,d   Rosenberg, E S ^a   Altfeld, M ^a   Walker, B D ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b FENWAY INSTITUTE   (United States)

^c LEMUEL SHATTUCK HOSPITAL   (United States)

^d JOHN RADCLIFFE HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; GAG PROTEIN; NEF PROTEIN; PROTEIN SUBUNIT;

ARTICLE; CELLULAR IMMUNITY; CONTROLLED STUDY; ENZYME LINKED IMMUNOSPOT ASSAY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; LABORATORY TEST; MAJOR CLINICAL STUDY; MOLECULAR RECOGNITION; MONONUCLEAR CELL; NONHUMAN; PRIORITY JOURNAL; T LYMPHOCYTE; VIRUS GENOME; VIRUS LOAD; VIRUS REPLICATION;

ACQUIRED IMMUNODEFICIENCY SYNDROME; AMINO ACID SEQUENCE; EPITOPES, T-LYMPHOCYTE; FEMALE; GENE PRODUCTS, NEF; GENOME, VIRAL; HIV CORE PROTEIN P24; HIV-1; HUMANS; INTERFERON TYPE II; MALE; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS; T-LYMPHOCYTES; VIRAL LOAD;

EID: 0037302428     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.77.3.2081-2092.2003     Document Type: Article

References (51)

1. Addo, M. M., M. Altfeld, A. Rathod, M. Yu, X. G. Yu, P. J. R. Goulder, E. S. Rosenberg, and B. D. Walker. 2002. HIV-1 Vpu represents a minor target for cytotoxic T lymphocytes (CTL) in HIV-1-infection. AIDS 16:1071-1073.
2. Addo, M. M., M. Altfeld, E. S. Rosenberg, R. L. Eldridge, M. N. Philips, K. Habeeb, A. Khatri, C. Brander, G. K. Robbins, G. P. Mazzara, P. J. Goulder, and B. D. Walker. 2001. The HIV-1 regulatory proteins Tat and Rev are frequently targeted by cytotoxic T lymphocytes derived from HIV-1-infected individuals. Proc. Natl. Acad. Sci. USA 98:1781-1786.
3. Allen, T. M., D. H. O'Connor, P. Jing, J. L. Dzuris, B. R. Mothe, T. U. Vogel, E. Dunphy, M. E. Liebl, C. Emerson, N. Wilson, K. J. Kunstman, X. Wang, D. B. Allison, A. L. Hughes, R. C. Desrosiers, J. D. Altman, S. M. Wolinsky, A. Sette, and D. I. Watkins. 2000. Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia. Nature 407: 386-390.
4. Altfeld, M., M. M. Addo, R. L. Eldridge, X. G. Yu, S. Thomas, A. Khatri, D. Strick, M. N. Phillips, G. B. Cohen, S. A. Islam, S. A. Kalams, C. Brander, P. J. Goulder, E. S. Rosenberg, and B. D. Walker. 2001. Vpr is preferentially targeted by CTL during HIV-1 infection. J. Immunol. 167:2743-2752.
5. Altfeld, M., E. S. Rosenberg, R. Shankarappa, J. S. Mukherjee, F. M. Hecht, R. L. Eldridge, M. M. Addo, S. H. Poon, M. N. Phillips, G. K. Robbins, P. E. Sax, S. Boswell, J. O. Kahn, C. Brander, P. J. Goulder, J. A. Levy, J. I. Mullins, and B. D. Walker. 2001. Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J. Exp. Med. 193:169-180.
6. Altfeld, M. A., A. Trocha, R. L. Eldridge, E. S. Rosenberg, M. N. Phillips, M. M. Addo, R. P. Sekaly, S. A. Kalams, S. A. Burchett, K. McIntosh, B. D. Walker, and P. J. Goulder. 2000. Identification of dominant optimal HLA-B60- and HLA-B61-restricted cytotoxic T-lymphocyte (CTL) epitopes: rapid characterization of CTL responses by enzyme-linked immunospot assay. J. Virol. 74:8541-8549.
7. Amara, R. R., F. Villinger, J. D. Altman, S. L. Lydy, S. P. O'Neil, S. I. Staprans, D. C. Montefiori, Y. Xu, J. G. Herndon, L. S. Wyatt, M. A. Candido, N. L. Kozyr, P. L. Earl, J. M. Smith, H. L. Ma, B. D. Grimm, M. L. Hulsey, J. Miller, H. M. McClure, J. M. McNicholl, B. Moss, and H. L. Robinson. 2001. Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science 292:69-74.
8. Appay, V., P. R. Dunbar, M. Callan, P. Klenerman, G. M. Gillespie, L. Papagno, G. S. Ogg, A. King, F. Lechner, C. A. Spina, S. Little, D. V. Havlir, D. D. Richman, N. Gruener, G. Pape, A. Waters, P. Easterbrook, M. Salio, V. Cerundolo, A. J. McMichael, and S. L. Rowland-Jones. 2002. Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat. Med. 8:379-385.
9. Barouch, D. H., J. Kunstman, M. J. Kuroda, J. E. Schmitz, S. Santra, F. W. Peyerl, G. R. Krivulka, K. Beaudry, M. A. Lifton, D. A. Gorgone, D. C. Montefiori, M. G. Lewis, S. M. Wolinsky, and N. L. Letvin. 2002. Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes. Nature 415:335-339.
10. Barouch, D. H., S. Santra, J. E. Schmitz, M. J. Kuroda, T. M. Fu, W. Wagner, M. Bilska, A. Craiu, X. X. Zheng, G. R. Krivulka, K. Beaudry, M. A. Lifton, C. E. Nickerson, W. L. Trigona, K. Punt, D. C. Freed, L. Guan, S. Dubey, D. Casimiro, A. Simon, M. E. Davies, M. Chastain, T. B. Strom, R. S. Gelman, D. C. Montefiori, M. G. Lewis, E. A. Emini, J. W. Shiver, and N. L. Letvin. 2000. Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. Science 290:486-492.
11. + T-cell responses: relationship to viral load in untreated HIV infection. J. Virol. 75:11983-11991.
12. +-T-cell responses cannot be predicted by major histocompatibility complex class I haplotype. J. Virol. 74:9144-9151.
13. + cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J. Virol. 68:6103-6110.
14. Borrow, P., H. Lewicki, X. Wei, M. S. Horwitz, N. Peffer, H. Meyers, J. A. Nelson, J. E. Gairin, B. H. Hahn, M. B. Oldstone, and G. M. Shaw. 1997. Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat. Med. 3:205-211.
15. Champagne, P., G. S. Ogg, A. S. King, C. Knabenhans, K. Ellefsen, M. Nobile, V. Appay, G. P. Rizzardi, S. Fleury, M. Lipp, R. Forster, S. Rowland-Jones, R. P. Sekaly, A. J. McMichael, and G. Pantaleo. 2001. Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature 410:106-111.
16. + responses in HIV type 1-infected patients: comparison with anti-Epstein-Barr virus responses and changes during antiretroviral therapy. J. Virol. 73:7108-7116.
17. Dalod, M., M. Harzic, I. Pellegrin, B. Dumon, B. Hoen, D. Sereni, J. C. Deschemin, J. P. Levy, A. Venet, and E. Gomard. 1998. Evolution of cytotoxic T lymphocyte responses to human immunodeficiency virus type 1 in patients with symptomatic primary infection receiving antiretroviral triple therapy. J. Infect. Dis. 178:61-69.
18. Day, C. L., A. K. Shea, M. A. Altfeld, D. P. Olson, S. P. Buchbinder, F. M. Hecht, E. S. Rosenberg, B. D. Walker, and S. A. Kalams. 2001. Relative dominance of epitope-specific cytotoxic T-lymphocyte responses in human immunodeficiency virus type 1-infected persons with shared HLA alleles. J. Virol. 75:6279-6291.
19. +-T-cell responses to the Gag protein of human immunodeficiency virus type 1 correlates inversely with viral load in plasma. J. Virol. 76:2298-2305.
20. Flanagan, K. L., E. A. Lee, M. B. Gravenor, W. H. Reece, B. C. Urban, T. Doherty, K. A. Bojang, M. Pinder, A. V. Hill, and M. Plebanski. 2001. Unique T cell effector functions elicited by Plasmodium falciparum epitopes in malaria-exposed Africans tested by three T cell assays. J. Immunol. 167:4729-4737.
21. Gea-Banacloche, J. C., S. A. Migueles, L. Martino, W. L. Shupert, A. C. McNeil, M. S. Sabbaghian, L. Ehler, C. Prussin, R. Stevens, L. Lambert, J. Altman, C. W. Hallahan, J. C. de Quiros, and M. Connors. 2000. Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors. J. Immunol. 165:1082-1092.
22. Goulder, P. J., M. M. Addo, M. A. Altfeld, E. S. Rosenberg, Y. Tang, U. Govender, N. Mngqundaniso, K. Annamalai, T. U. Vogel, M. Hammond, M. Bunce, H. M. Coovadia, and B. D. Walker. 2001. Rapid definition of five novel HLA-A*3002-restricted human immunodeficiency virus-specific cytotoxic T-lymphocyte epitopes by Elispot and intracellular cytokine staining assays. J. Virol. 75:1339-1347.
23. Goulder, P. J., C. Brander, Y. Tang, C. Tremblay, R. A. Colbert, M. M. Addo, E. S. Rosenberg, T. Nguyen, R. Allen, A. Trocha, M. Altfeld, S. He, M. Bunce, R. Funkhouser, S. I. Pelton, S. K. Burchett, K. McIntosh, B. T. Korber, and B. D. Walker. 2001. Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412:334-338.
24. Goulder, P. J., R. E. Phillips, R. A. Colbert, S. McAdam, G. Ogg, M. A. Nowak, P. Giangrande, G. Luzzi, B. Morgan, A. Edwards, A. J. McMichael, and S. Rowland-Jones. 1997. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat. Med. 3:212-217.
25. Goulder, P. J., Y. Tang, S. I. Pelton, and B. D. Walker. 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.
26. Harrer, T., E. Harrer, S. A. Kalams, T. Elbeik, S. I. Staprans, M. B. Feinberg, Y. Cao, D. D. Ho, T. Yilma, A. M. Caliendo, R. P. Johnson, S. P. Buchbinder, and B. D. Walker. 1996. Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection. AIDS Res. Hum. Retrovir. 12:585-592.
27. + T cell depletion in simian immunodeficiency virus-infected macaques. J. Exp. Med. 189:991-998.
28. +-T-cell response to human cytomegalovirus: the 72-kilodalton major immediate-early protein revisited. J. Virol. 73:8179-8184.
29. Klein, M. R., C. A. van Baalen, A. M. Holwerda, S. R. Kerkhof Garde, R. J. Bende, I. P. Keet, J. K. Eeftinck-Schattenkerk, A. D. Osterhaus, H. Schuitemaker, and F. Miedema. 1995. Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics. J. Exp. Med. 181:1365-1372.
30. Konopitzky, R., U. Konig, R. G. Meyer, W. Sommergruber, T. Wolfel, and T. Schweighoffer. 2002. Identification of HLA-A*0201-restricted T Cell epitopes derived from the novel overexpressed tumor antigen calcium-activated chloride channel 2. J. Immunol. 169:540-547.
31. Koup, R. A., J. T. Safrit, Y. Cao, C. A. Andrews, G. McLeod, W. Borkowsky, C. Farthing, and D. D. Ho. 1994. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J. Virol. 68:4650-4655.
32. Larsson, M., D. Messmer, S. Somersan, J. F. Fonteneau, S. M. Donahoe, M. Lee, P. R. Dunbar, V. Cerundolo, I. Julkunen, D. F. Nixon, and N. Bhardwaj. 2000. Requirement of mature dendritic cells for efficient activation of influenza A-specific memory CD8+ T cells. J. Immunol. 165:1182-1190.
33. Larsson, M., D. T. Wilkens, J. F. Fonteneau, T. J. Beadle, M. J. Merritt, R. G. Kost, P. A. Haslett, S. Cu-Uvin, N. Bhardwaj, D. F. Nixon, and B. L. Shacklett. 2002. Amplification of low-frequency antiviral CD8 T cell responses using autologous dendritic cells. AIDS 16:171-180.
34. +-T-cell responses against hepatitis C virus reveals multiple unpredicted specificities. J. Virol. 76:6104-6113.
35. McMichael, A. J., and S. L. Rowland-Jones. 2001. Cellular immune responses to HIV. Nature 410:980-987.
36. Mothe, B. R., H. Horton, D. K. Carter, T. M. Allen, M. E. Liebl, P. Skinner, T. U. Vogel, S. Fuenger, K. Vielhuber, W. Rehrauer, N. Wilson, G. Franchini, J. D. Altman, A. Haase, L. J. Picker, D. B. Allison, and D. I. Watkins. 2002. Dominance of CD8 responses specific for epitopes bound by a single major histocompatibility complex class I molecule during the acute phase of viral infection. J. Virol. 76:875-884.
37. Ogg, G. S., X. Jin, S. Bonhoeffer, P. R. Dunbar, M. A. Nowak, S. Monard, J. P. Segal, Y. Cao, S. L. Rowland-Jones, V. Cerundolo, A. Hurley, M. Markowitz, D. D. Ho, D. F. Nixon, and A. J. McMichael. 1998. Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 279:2103-2106.
38. Pitcher, C. J., C. Quittner, D. M. Peterson, M. Connors, R. A. Koup, V. C. Maino, and L J. Picker. 1999. HIV-1-specific CD4+ T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression. Nat. Med. 5:518-525.
39. Pittet, M. J., A. Zippelius, D. E. Speiser, M. Assenmacher, P. Guillaume, D. Valmori, D. Lienard, F. Lejeune, J. C. Cerottini, and P. Romero. 2001. Ex vivo IFN-gamma secretion by circulating CD8 T lymphocytes: implications of a novel approach for T cell monitoring in infectious and malignant diseases. J. Immunol. 166:7634-7640.
40. Price, P., R. P. Johnson, D. T. Scadden, C. Jassoy, T. Rosenthal, S. Kalams, and B. D. Walker. 1995. Cytotoxic CD8+ T lymphocytes reactive with human immunodeficiency virus-1 produce granulocyte/macrophage colony-stimulating factor and variable amounts of interleukins 2, 3, and 4 following stimulation with the cognate epitope. Clin. Immunol. Immunopathol. 74:100-106.
41. Rosenberg, E. S., J. M. Billingsley, A. M. Caliendo, S. L. Boswell, P. E. Sax, S. A. Kalams, and B. D. Walker. 1997. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 278:1447-1450.
42. Rowland-Jones, S. L., S. Pinheiro, R. Kaul, P. Hansasuta, G. Gillespie, T. Dong, F. A. Plummer, J. B. Bwayo, S. Fidler, J. Weber, A. McMichael, and V. Appay. 2001. How important is the 'quality' of the cytotoxic T lymphocyte (CTL) response in protection against HIV infection? Immunol. Lett. 79:1520.
43. Schmitz, J. E., M. J. Kuroda, S. Santra, V. G. Sasseville, M. A. Simon, M. A. Lifton, P. Racz, K. Tenner-Racz, M. Dalesandro, B. J. Scallon, J. Ghrayeb, M. A. Forman, D. C. Montefiori, E. P. Rieber, N. L. Letvin, and K. A. Reimann. 1999. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283:857-860.
44. Shiver, J. W., T. M. Fu, L. Chen, D. R. Casimiro, M. E. Davies, R. K. Evans, Z. Q. Zhang, A. J. Simon, W. L. Trigona, S. A. Dubey, L. Huang, V. A. Harris, R. S. Long, X. Liang, L. Handt, W. A. Schleif, L. Zhu, D. C. Freed, N. V. Persaud, L. Guan, K. S. Punt, A. Tang, M. Chen, K. A. Wilson, K. B. Collins, G. J. Heidecker, V. R. Fernandez, H. C. Perry, J. G. Joyce, K. M. Grimm, J. C. Cook, P. M. Keller, D. S. Kresock, H. Mach, R. D. Troutman, L. A. Isopi, D. M. Williams, Z. Xu, K. E. Bohannon, D. B. Volkin, D. C. Montefiori, A. Miura, G. R. Krivulka, M. A. Lifton, M. J. Kuroda, J. E. Schmitz, N. L. Letvin, M. J. Caulfield, A. J. Bett, R. Youil, D. C. Kaslow, and E. A. Emini. 2002. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 415:331-335.
45. Stern, B. V., B. O. Boehm, and M. Tary-Lehmann. 2002. Vaccination with tumor peptide in CpG adjuvant protects via IFN-gamma-dependent CD4 cell immunity. J. Immunol. 168:6099-6105.
46. , van Baalen, C. A., O. Pontesilli, R. C. Huisman, A. M. Geretti, M. R. Klein, F. de Wolf, F. Miedema, R. A. Gruters, and A. D. Osterhaus. 1997. Human immunodeficiency virus type 1 Rev- and Tat-specific cytotoxic T lymphocyte frequencies inversely correlate with rapid progression to AIDS. J. Gen. Virol. 78:1913-1918.
47. Walker, B. D., S. Chakrabarti, B. Moss, T. J. Paradis, T. Flynn, A. G. Durno, R. S. Blumberg, J. C. Kaplan, M. S. Hirsch, and R. T. Schooley. 1987. HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature 328:345-348.
48. + responses to Epstein-Barr virus antigens. Blood 95:241-248.
49. Yu, X. G., M. M. Addo, E. S. Rosenberg, W. R. Rodriguez, P. K. Lee, C. A. Fitzpatrick, M. N. Johnston, D. Strick, P. J. Goulder, B. D. Walker, and M. Altfeld. 2002. Consistent patterns in the development and immunodominance of human immunodeficiency virus type 1(HIV-1)-specific CD8(+)T-cell responses following acute HIV-1 infection. J. Virol. 76:8690-8701.
50. Yu, X. G., H. Shang, M. M. Addo, R. L. Eldridge, M. N. Phillips, M. E. Feeney, D. Strick, C. Brander, P. J. Goulder, E. S. Rosenberg, B. D. Walker, and M. Altfeld. 2002. Important contribution of p15 Gag-specific responses to the total Gag-specific CTL responses. AIDS 16:321-328.
51. Yusim, K., C. Kesmir, B. Gaschen, M. M. Addo, M. Altfeld, S. Brunak, A. Chigaev, V. Detours, and B. T. Korber. 2002. Clustering patterns of cytotoxic T-lymphocyte epitopes in human immunodeficiency virus type 1(HIV-1) proteins reveal imprints of immune evasion on HIV-1 global variation. J. Virol. 76:8757-8768.