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Journal of General Virology header logo Journal of General Virology

Volume 78, Issue 9

Primary induction of human cytotoxic lymphocytes against a synthetic peptide of the human immunodeficiency virus type 1 protease No Access

Abstract

Identification of immunogenicT-cell epitopes is important for the design of immunotherapeutics targeted to specific antigenic sites. To identify candidate cytotoxic T-lymphocyte (CTL) epitopes in the protease of human immunodeficiency virus type 1 (HIV-1) strain MN, we synthesized 9-mer and 10- mer peptides containing the HLA-A*0201 binding motif. Binding affinity of the peptides was measured by HLA-A*0201 up-regulation on T2 cells. Peptides with high binding-affinity were tested for their ability to stimulate primary CTLs from healthy HIVnegative blood donors. Peptide-specific CTLs were obtained from five out of six donors by stimulation with a 9-mer (LVGPTPVNI) or a 10-mer (VLVGPTPVNI) peptide derived from a highly conserved amino acid stretch in the C-terminal region of the protease. Addition of peptide-specific CTLs to acutely HIV-infected lymphocytes resulted in inhibition of p24 production. In conclusion, a highly conserved HIV protease peptide regularly elicits peptide-specific CTLs. Targeting immune responses against defined epitopes in non-variable regions may be a feasible way to minimize the risk of virus escape from immune surveillance.

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© Society for General Microbiology 1997
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1997-09-01
2025-11-11

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References

  1. Baier M., Werner A., Bannert N., Metzner K., Kurth R. 1995; HIV suppression by interleukin-16. Nature 37:563
     [Google Scholar]
  2. Cocchi F., De Vico A. L., Garzino-Demo A., Arya S. K., Gallo R. C., Lusso P. 1995; Identification of RANTES, MIP-1α and MIP-1α as major HIV-suppressive factors produced by CD8+ T cells. Science 27:1811–1815
     [Google Scholar]
  3. Couillin I., Connan F., Culmannpenciolelli B., Gomard E., Guillet J. G., Choppin J. 1995; HLA-dependent variations in human immunodeficiency virus Nef protein alter peptide HLA binding. European Journal of Immunology 25:728–732
     [Google Scholar]
  4. Croft M. 1994; Activation of naive, memory and effector T cells. Current Opinion in Immunology 6:413–437
     [Google Scholar]
  5. del Guercio M. F., Sidney J., Hermanson G., Perez C., Grey H. M., Kubo R. T., Sette A. 1995; Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype. Journal of Immunology 154:685–693
     [Google Scholar]
  6. Demaria A., Cirillo C., Moretta L. 1994; Occurrence of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic T cell activity in apparently uninfected children born to HIV-1-infected mothers. Journal of Infectious Diseases 170:1296–1299
     [Google Scholar]
  7. Gotch F., Rothbard J., Howland K., Townsend A., McMichael A. 1987; Cytotoxic T lymphocytes recognize a fragment of influenza virus matrix protein in association with HLA-A2. Nature 326:881–882
     [Google Scholar]
  8. Harrer E., Harrer T., Barbosa P., Feinberg M., Johnson R. P., Buchbinder S., Walker B. D. 1996a; Recognition of the highly conserved YMDD region in the human immunodeficiency virus type 1 reverse transcriptase by HLA-A2-restricted cytotoxic T lymphocytes from an asymptomatic long-term nonprogressor. Journal of Infectious Diseases 173:476–479
     [Google Scholar]
  9. Harrer T., Harrer E., Kalams S. A., Barbosa P., Trocha A., Johnson R. P., Elbeik T., Feinberg M. B., Buchbinder S., Walker B. D. 1996b; Cytotoxic T lymphocytes in asymptomatic long-term nonprogressing HIV-1 infection. Journal of Immunology 156:2616–2623
     [Google Scholar]
  10. Ho M., Armstrong J., McMahon D., Pazin G., Huang X. L., Rinaldo C., Whiteside T., Tripoli C., Levine G., Moody D. others 1993; A phase 1 study of adoptive transfer of autologous CD8 + T lymphocytes in patients with acquired immunodeficiency syndrome (AIDS)-related complex or AIDS. Blood 81:2093–2101
     [Google Scholar]
  11. Hsueh F. W., Walker C. M., Blackbourn D. J., Levy J. A. 1994; Suppression of HIV replication by CD8+ cell clones derived from HIV-infected and uninfected individuals. Cellular Immunology 159:271–279
     [Google Scholar]
  12. Irwin M. J., Heath W. R., Sherman L. A. 1989; Species restricted interactions between CD8 and a3 domain of class I influence the magnitude of xenogenic response. Journal of Experimental Medicine 170:1091–1101
     [Google Scholar]
  13. Kageyama S., Tsomides T. J., Sykulev Y., Eisen H. N. 1995; Variations in the number of peptide-MHC class I complexes required to activate cytotoxic T cell responses. Journal of Immunology 154:567–576
     [Google Scholar]
  14. Kast W. M., Brandt R. M., Sidney J., Drijfhout J. W., Kubo R. T., Grey H. M., Melief C. J., Sette A. 1994; Role of HLA-A motifs in identification of potential CTL epitopes in human papillomavirus type 16 E6 and E7 proteins. Journal of Immunology 152:3904–3912
     [Google Scholar]
  15. Klenerman P., Rowland-Jones S. L., McAdam S., Edwards J., Daenke S., Lalloo D., Koppe B., Rosenberg W., Boyd D., Edwards A. others 1994; Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants. Nature 369:403–407
     [Google Scholar]
  16. Koup R. A., Safrit J. T., Cao Y. Z., Andrews C. A., McLeod G., Borkowsky W., Farthing C., Ho D. D. 1994; Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. Journal of Virology 68:4650–4655
     [Google Scholar]
  17. Lamhamedicherradi S., Culmannpenciolelli B., Guy B., Ly T. D., Goujard C., Guillet J. G., Gomard E. 1995; Different patterns of HIV-1-specific cytotoxic T-lymphocyte activity after primary infection. AIDS 9:421–426
     [Google Scholar]
  18. Langlade D. P., Ngo-Giang-Huong N., Ferchal F., Oksenhendler E. 1994; Human immunodeficiency virus (HIV) Nef-specific cytotoxic T lymphocytes in noninfected heterosexual contact of HIV-infected patients. Journal of Clinical Investigation 93:1293–1297
     [Google Scholar]
  19. Levy J. A. 1995; HIV research: a need to focus on the right target. Lancet 345:1619–1621
     [Google Scholar]
  20. Levy J. A. 1996; Controlling HIV pathogenesis: the role of the noncytotoxic anti-HIV response of CD8 + T cells. Immunology Today 17:217–224
     [Google Scholar]
  21. Macatonia S. E., Patterson S., Knight S. C. 1991; Primary proliferative and cytotoxic T-cell responses to HIV induced in vitro by human dendritic cells. Immunology 74:399–406
     [Google Scholar]
  22. Mackewicz C. E., Blackbourn D. J., Levy J. A. 1995; CD8 + T cells suppress human immunodeficiency virus replication by inhibiting viral transcription. Proceedings of the National Academy of Sciences, USA 92:2308–2312
     [Google Scholar]
  23. Moss P., Rowland-Jones S. L., Frodsham P. M., McAdam S., Giangrande P., McMichael A. J., Bell J. I. 1995; Persistent high frequency of human immunodeficiency virus-specific cytotoxic T cells in peripheral blood of infected donors. Proceedings ofthe National Academy of Sciences, USA 92:5773–5777
     [Google Scholar]
  24. Myers G., Wain-Hobson S., Henderson L. E., Korber B., Kuan-Teh J., Pavlakis G. N. 1996 Compilation and analysis of nucleic acid and amino acid sequences. Human retroviruses and AIDS Theoretical Biology and Biophysics, Los Alamos National Library, Los Alamos, New Mexico, USA: Internet location: http://hiv-web.lanl.gov/
    [Google Scholar]
  25. Nowak M. A., May R. M., Phillips R. E., Rowland-Jones S. L., Lalloo D. G., McAdam S., Klenerman P., Koppe B., Sigmund K., Bangham C., McMichael A. J. 1995; Antig enic oscillations and shifting immunodominance in HIV-1 infections. Nature 375:606–611
     [Google Scholar]
  26. Phillips R. E., Rowland-Jones S. L., Nixon D. F., Gotch F. M., Edwards J. P., Ogunlesi A. O., Elvin J. G., Rothbard J. A., Bangham C. R., Rizza C. R. others 1991; Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature 354:453–459
     [Google Scholar]
  27. Pinto L. A., Sullivan J., Berzofsky J. A., Clerici M., Kessler H. A., Landay A. L., Shearer G. M. 1995; Env-specific cytotoxic T lymphocyte responses in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids. Journal of Clinical Investigation 96:867–876
     [Google Scholar]
  28. Ressing M. E., Sette A., Brandt R. M., Ruppert J., Wentworth P. A., Hartman M., Oseroff C., Grey H. M., Melief C. J., Kast W. M. 1995; Human CTL epitopes encoded by human papillomavirus type 16 E6 and E7 identified through in vivo and in vitro immunogenicity studies of HLA-A*0201-binding peptides. Journal of Immunology 154:5934–5943
     [Google Scholar]
  29. Rowland-Jones S. L., McMichael A. 1995; Immune responses in HIV-exposed seronegatives - have they repelled the virus?. Current Opinion in Immunology 7:448–455
     [Google Scholar]
  30. Rowland-Jones S. L., Sutton J., Ariyoshi K., Dong T., Gotch F., McAdam S., Whitby D., Sabally S., Gallimore A., Corrah T., Takiguchi M., Schultz T., McMichael A., Whittle H. 1995; HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women. Nature Medicine 1:59–64
     [Google Scholar]
  31. Salter R. D., Cresswell P. 1986; Impairedassembly andtransport of HLA-A and -B antigens in a mutant T × B cell hybrid. EMBO Journal 5:943–949
     [Google Scholar]
  32. Stuber G., Dillner J., Modrow S., Wolf H., Szekely L., Klein G., Klein E. 1995; HLA-A0201 and HLA-B7 binding peptides in the EBV-encoded EBNA-1, EBNA-2 and BZLF-1 proteins detected in the MHC class I stabilization assay. Low proportion of binding motifs for several HLA class I alleles in EBNA-1. International Immunology 7:653–663
     [Google Scholar]
  33. Sundqvist V. A., Albert J., Ohlsson E., Hinkula J., Fenyö E. M., Wahren B. 1989; Human immunodeficiency virus type 1 p24 production and antigenic variation in tissue culture of isolates with various growth characteristics. Journal of Medical Virology 29:170–175
     [Google Scholar]
  34. Tsubota H., Lord C. I., Watkins D. I., Morimoto C., Letvin N. L. 1989; A cytotoxic T lymphocyte inhibits acquired immunodeficiency syndrome virus replication in peripheral blood lymphocytes. Journal of Experimental Medicine 169:1421–1434
     [Google Scholar]
  35. Vanderburg S. H., Klein M. R., Vandevelde C., Kast W. M., Miedema F., Melief C. 1995; Induction of a primary human cytotoxic T-lymphocyte response against a novel conserved epitope in a functional sequence of HIV-1 reverse transcriptase. AIDS 9:121–127
     [Google Scholar]
  36. Vitiello A., Ishioka G., Grey H. M., Rose R., Farness P., LaFond R., Yuan L., Chisari F. V., Furze J., Bartholomeuz R. others 1995; Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans. Journal of Clinical Investigation 95:341–349
     [Google Scholar]
  37. Walker B. D., Chakrabarti S., Moss B., Paradis T. J., Flynn T., Durno A. G., Blumberg R. S., Kaplan J. C., Hirsch M. S., Schooley R. T. 1987; HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature 328:345–348
     [Google Scholar]
  38. Walker B. D., Flexner C., Paradis T. J., Fuller T. C., Hirsch M. S., Schooley R. T., Moss B. 1988; HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals. Science 240:64–66
     [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-78-9-2217
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Primary induction of human cytotoxic lymphocytes against a synthetic peptide of the human immunodeficiency virus type 1 protease
J. Gen. Virol. 78, 2217 (1997); https://doi.org/10.1099/0022-1317-78-9-2217
/content/journal/jgv/10.1099/0022-1317-78-9-2217
/content/journal/jgv/10.1099/0022-1317-78-9-2217
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