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. 1996 Oct;70(10):6741–6750. doi: 10.1128/jvi.70.10.6741-6750.1996

Induction of anti-gp160 cytotoxic T cells cross-reacting with various V3 loop P18 peptides in human immunodeficiency virus type 1 envelope-immunized individuals.

A Achour 1, F Bex 1, P Hermans 1, A Burny 1, D Zagury 1
PMCID: PMC190717  PMID: 8794311

Abstract

Cytotoxic T lymphocytes (CTL) may be important to prevent cell-to-cell transmission of human immunodeficiency virus type 1 (HIV-1), the agent responsible for AIDS. In this study, we investigated the epitope specificity of CTLs induced in individuals immunized against the virus envelope glycoprotein gp160. The determinant of HIV-1 gp160 for the stimulation of CTL is located in a region of high sequence variability among HIV-1 isolates, the so-called V3 loop P18. Using a panel of P18 peptides, we compared the CTL specificities of cells from two individuals immunized with vaccinia virus recombinants expressing the envelope glycoproteins from two different strains of HIV-1, IIIB and SIMI. For this purpose, CTLs specific for the IIIB P18 peptide (RIQRGPGRAFVTIGK) were compared with CTLs for the site from the SIMI isolate (TLHMGPKRAFYATGD). The results indicate that in contrast to CD8+ CTLs induced by the glycoprotein from strain IIIB, CD8+ CTLs induced by strain SIMI strongly cross-reacted with targets presenting P18 peptides as well as envelope proteins from the divergent MN and RF isolates but failed to cross-react with targets that presented the IIIB peptide. These data have implications for the design of an HIV vaccine.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Achour A., Lemhammedi S., Picard O., M'Bika J. P., Zagury J. F., Moukrim Z., Willer A., Beix F., Burny A., Zagury D. Cytotoxic T lymphocytes specific for HIV-1 gp160 antigen and synthetic P18IIIB peptide in an HLA-A11-immunized individual. AIDS Res Hum Retroviruses. 1994 Jan;10(1):19–25. doi: 10.1089/aid.1994.10.19. [DOI] [PubMed] [Google Scholar]
  2. Achour A., Picard O., Mbika J. P., Willer A., Snart R., Bizzini B., Carelli C., Burny A., Zagury D. Envelope protein and p18(IIIB) peptide recognized by cytotoxic T lymphocytes from humans immunized with human immunodeficiency virus envelope. Vaccine. 1993;11(7):609–701. doi: 10.1016/0264-410x(93)90251-r. [DOI] [PubMed] [Google Scholar]
  3. Achour A., Picard O., Zagury D., Sarin P. S., Gallo R. C., Naylor P. H., Goldstein A. L. HGP-30, a synthetic analogue of human immunodeficiency virus (HIV) p17, is a target for cytotoxic lymphocytes in HIV-infected individuals. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7045–7049. doi: 10.1073/pnas.87.18.7045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Alexander M. A., Damico C. A., Wieties K. M., Hansen T. H., Connolly J. M. Correlation between CD8 dependency and determinant density using peptide-induced, Ld-restricted cytotoxic T lymphocytes. J Exp Med. 1991 Apr 1;173(4):849–858. doi: 10.1084/jem.173.4.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berman P. W., Gregory T. J., Riddle L., Nakamura G. R., Champe M. A., Porter J. P., Wurm F. M., Hershberg R. D., Cobb E. K., Eichberg J. W. Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. Nature. 1990 Jun 14;345(6276):622–625. doi: 10.1038/345622a0. [DOI] [PubMed] [Google Scholar]
  6. Bex F., Hermans P., Sprecher S., Achour A., Badjou R., Desgranges C., Cogniaux J., Franchioli P., Vanhulle C., Lachgar A. Syngeneic adoptive transfer of anti-human immunodeficiency virus (HIV-1)-primed lymphocytes from a vaccinated HIV-seronegative individual to his HIV-1-infected identical twin. Blood. 1994 Nov 15;84(10):3317–3326. [PubMed] [Google Scholar]
  7. Buseyne F., McChesney M., Porrot F., Kovarik S., Guy B., Rivière Y. Gag-specific cytotoxic T lymphocytes from human immunodeficiency virus type 1-infected individuals: Gag epitopes are clustered in three regions of the p24gag protein. J Virol. 1993 Feb;67(2):694–702. doi: 10.1128/jvi.67.2.694-702.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cao Y., Qin L., Zhang L., Safrit J., Ho D. D. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med. 1995 Jan 26;332(4):201–208. doi: 10.1056/NEJM199501263320401. [DOI] [PubMed] [Google Scholar]
  9. Carmichael A., Jin X., Sissons P., Borysiewicz L. Quantitative analysis of the human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein-Barr virus in late disease. J Exp Med. 1993 Feb 1;177(2):249–256. doi: 10.1084/jem.177.2.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Clerici M., Lucey D. R., Zajac R. A., Boswell R. N., Gebel H. M., Takahashi H., Berzofsky J. A., Shearer G. M. Detection of cytotoxic T lymphocytes specific for synthetic peptides of gp160 in HIV-seropositive individuals. J Immunol. 1991 Apr 1;146(7):2214–2219. [PubMed] [Google Scholar]
  11. Clerici M., Stocks N. I., Zajac R. A., Boswell R. N., Bernstein D. C., Mann D. L., Shearer G. M., Berzofsky J. A. Interleukin-2 production used to detect antigenic peptide recognition by T-helper lymphocytes from asymptomatic HIV-seropositive individuals. Nature. 1989 Jun 1;339(6223):383–385. doi: 10.1038/339383a0. [DOI] [PubMed] [Google Scholar]
  12. Clerici M., Tacket C. O., Via C. S., Lucey D. R., Muluk S. C., Zajac R. A., Boswell R. N., Berzofsky J. A., Shearer G. M. Immunization with subunit human immunodeficiency virus vaccine generates stronger T helper cell immunity than natural infection. Eur J Immunol. 1991 Jun;21(6):1345–1349. doi: 10.1002/eji.1830210603. [DOI] [PubMed] [Google Scholar]
  13. Culmann B., Gomard E., Kiény M. P., Guy B., Dreyfus F., Saimot A. G., Sereni D., Sicard D., Lévy J. P. Six epitopes reacting with human cytotoxic CD8+ T cells in the central region of the HIV-1 NEF protein. J Immunol. 1991 Mar 1;146(5):1560–1565. [PubMed] [Google Scholar]
  14. Earl P. L., Moss B., Morrison R. P., Wehrly K., Nishio J., Chesebro B. T-lymphocyte priming and protection against Friend leukemia by vaccinia-retrovirus env gene recombinant. Science. 1986 Nov 7;234(4777):728–731. doi: 10.1126/science.3490689. [DOI] [PubMed] [Google Scholar]
  15. Girard M., Kieny M. P., Pinter A., Barre-Sinoussi F., Nara P., Kolbe H., Kusumi K., Chaput A., Reinhart T., Muchmore E. Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):542–546. doi: 10.1073/pnas.88.2.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goodenow M., Huet T., Saurin W., Kwok S., Sninsky J., Wain-Hobson S. HIV-1 isolates are rapidly evolving quasispecies: evidence for viral mixtures and preferred nucleotide substitutions. J Acquir Immune Defic Syndr. 1989;2(4):344–352. [PubMed] [Google Scholar]
  17. Gotch F., McMichael A., Smith G., Moss B. Identification of viral molecules recognized by influenza-specific human cytotoxic T lymphocytes. J Exp Med. 1987 Feb 1;165(2):408–416. doi: 10.1084/jem.165.2.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hammond S. A., Bollinger R. C., Stanhope P. E., Quinn T. C., Schwartz D., Clements M. L., Siliciano R. F. Comparative clonal analysis of human immunodeficiency virus type 1 (HIV-1)-specific CD4+ and CD8+ cytolytic T lymphocytes isolated from seronegative humans immunized with candidate HIV-1 vaccines. J Exp Med. 1992 Dec 1;176(6):1531–1542. doi: 10.1084/jem.176.6.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hammond S. A., Obah E., Stanhope P., Monell C. R., Strand M., Robbins F. M., Bias W. B., Karr R. W., Koenig S., Siliciano R. F. Characterization of a conserved T cell epitope in HIV-1 gp41 recognized by vaccine-induced human cytolytic T cells. J Immunol. 1991 Mar 1;146(5):1470–1477. [PubMed] [Google Scholar]
  20. Johnson R. P., Trocha A., Buchanan T. M., Walker B. D. Identification of overlapping HLA class I-restricted cytotoxic T cell epitopes in a conserved region of the human immunodeficiency virus type 1 envelope glycoprotein: definition of minimum epitopes and analysis of the effects of sequence variation. J Exp Med. 1992 Apr 1;175(4):961–971. doi: 10.1084/jem.175.4.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Johnson R. P., Trocha A., Yang L., Mazzara G. P., Panicali D. L., Buchanan T. M., Walker B. D. HIV-1 gag-specific cytotoxic T lymphocytes recognize multiple highly conserved epitopes. Fine specificity of the gag-specific response defined by using unstimulated peripheral blood mononuclear cells and cloned effector cells. J Immunol. 1991 Sep 1;147(5):1512–1521. [PubMed] [Google Scholar]
  22. Klenerman P., Rowland-Jones S., McAdam S., Edwards J., Daenke S., Lalloo D., Köppe B., Rosenberg W., Boyd D., Edwards A. Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants. Nature. 1994 Jun 2;369(6479):403–407. doi: 10.1038/369403a0. [DOI] [PubMed] [Google Scholar]
  23. McMichael A. J., Gotch F., Cullen P., Askonas B., Webster R. G. The human cytotoxic T cell response to influenza A vaccination. Clin Exp Immunol. 1981 Feb;43(2):276–284. [PMC free article] [PubMed] [Google Scholar]
  24. Nakajima P. B., Betz C. J., Hansburg D. Expression of identical V alpha V beta gene pairs by IE-alloreactive and IE-restricted, antigen-specific T cells from MHC disparate mice. Evidence for thymic selection of V(D)J combinations. J Immunol. 1990 Jan 1;144(1):348–357. [PubMed] [Google Scholar]
  25. Nowak M. A., May R. M., Anderson R. M. The evolutionary dynamics of HIV-1 quasispecies and the development of immunodeficiency disease. AIDS. 1990 Nov;4(11):1095–1103. doi: 10.1097/00002030-199011000-00007. [DOI] [PubMed] [Google Scholar]
  26. Oldstone M. B., Blount P., Southern P. J., Lampert P. W. Cytoimmunotherapy for persistent virus infection reveals a unique clearance pattern from the central nervous system. Nature. 1986 May 15;321(6067):239–243. doi: 10.1038/321239a0. [DOI] [PubMed] [Google Scholar]
  27. Orentas R. J., Hildreth J. E., Obah E., Polydefkis M., Smith G. E., Clements M. L., Siliciano R. F. Induction of CD4+ human cytolytic T cells specific for HIV-infected cells by a gp160 subunit vaccine. Science. 1990 Jun 8;248(4960):1234–1237. doi: 10.1126/science.2190315. [DOI] [PubMed] [Google Scholar]
  28. Pantaleo G., De Maria A., Koenig S., Butini L., Moss B., Baseler M., Lane H. C., Fauci A. S. CD8+ T lymphocytes of patients with AIDS maintain normal broad cytolytic function despite the loss of human immunodeficiency virus-specific cytotoxicity. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4818–4822. doi: 10.1073/pnas.87.12.4818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Phillips R. E., Rowland-Jones S., Nixon D. F., Gotch F. M., Edwards J. P., Ogunlesi A. O., Elvin J. G., Rothbard J. A., Bangham C. R., Rizza C. R. Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature. 1991 Dec 12;354(6353):453–459. doi: 10.1038/354453a0. [DOI] [PubMed] [Google Scholar]
  30. Picard O., Achour A., Bernard J., Halbreich A., Bizzini B., Boyer V., Desgranges C., Bertho J. M., Lachgar A., Polliotti B. A 2-year follow-up of an anti-HIV immune reaction in HIV-1 gp160-immunized healthy seronegative humans: evidence for persistent cell-mediated immunity. J Acquir Immune Defic Syndr. 1992;5(6):539–546. [PubMed] [Google Scholar]
  31. Pircher H., Moskophidis D., Rohrer U., Bürki K., Hengartner H., Zinkernagel R. M. Viral escape by selection of cytotoxic T cell-resistant virus variants in vivo. Nature. 1990 Aug 16;346(6285):629–633. doi: 10.1038/346629a0. [DOI] [PubMed] [Google Scholar]
  32. Shirai M., Pendleton C. D., Ahlers J., Takeshita T., Newman M., Berzofsky J. A. Helper-cytotoxic T lymphocyte (CTL) determinant linkage required for priming of anti-HIV CD8+ CTL in vivo with peptide vaccine constructs. J Immunol. 1994 Jan 15;152(2):549–556. [PubMed] [Google Scholar]
  33. Shirai M., Pendleton C. D., Berzofsky J. A. Broad recognition of cytotoxic T cell epitopes from the HIV-1 envelope protein with multiple class I histocompatibility molecules. J Immunol. 1992 Mar 15;148(6):1657–1667. [PubMed] [Google Scholar]
  34. Takahashi H., Germain R. N., Moss B., Berzofsky J. A. An immunodominant class I-restricted cytotoxic T lymphocyte determinant of human immunodeficiency virus type 1 induces CD4 class II-restricted help for itself. J Exp Med. 1990 Feb 1;171(2):571–576. doi: 10.1084/jem.171.2.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Takahashi H., Houghten R., Putney S. D., Margulies D. H., Moss B., Germain R. N., Berzofsky J. A. Structural requirements for class I MHC molecule-mediated antigen presentation and cytotoxic T cell recognition of an immunodominant determinant of the human immunodeficiency virus envelope protein. J Exp Med. 1989 Dec 1;170(6):2023–2035. doi: 10.1084/jem.170.6.2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Takahashi H., Merli S., Putney S. D., Houghten R., Moss B., Germain R. N., Berzofsky J. A. A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160. Science. 1989 Oct 6;246(4926):118–121. doi: 10.1126/science.2789433. [DOI] [PubMed] [Google Scholar]
  37. Takahashi H., Nakagawa Y., Pendleton C. D., Houghten R. A., Yokomuro K., Germain R. N., Berzofsky J. A. Induction of broadly cross-reactive cytotoxic T cells recognizing an HIV-1 envelope determinant. Science. 1992 Jan 17;255(5042):333–336. doi: 10.1126/science.1372448. [DOI] [PubMed] [Google Scholar]
  38. Taylor P. M., Askonas B. A. Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo. Immunology. 1986 Jul;58(3):417–420. [PMC free article] [PubMed] [Google Scholar]
  39. Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
  40. Tsubota H., Lord C. I., Watkins D. I., Morimoto C., Letvin N. L. A cytotoxic T lymphocyte inhibits acquired immunodeficiency syndrome virus replication in peripheral blood lymphocytes. J Exp Med. 1989 Apr 1;169(4):1421–1434. doi: 10.1084/jem.169.4.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Van Bleek G. M., Nathenson S. G. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature. 1990 Nov 15;348(6298):213–216. doi: 10.1038/348213a0. [DOI] [PubMed] [Google Scholar]
  42. Walker C. M., Moody D. J., Stites D. P., Levy J. A. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science. 1986 Dec 19;234(4783):1563–1566. doi: 10.1126/science.2431484. [DOI] [PubMed] [Google Scholar]
  43. Yap K. L., Ada G. L., McKenzie I. F. Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature. 1978 May 18;273(5659):238–239. doi: 10.1038/273238a0. [DOI] [PubMed] [Google Scholar]
  44. Zagury D., Bernard J., Cheynier R., Desportes I., Leonard R., Fouchard M., Reveil B., Ittele D., Lurhuma Z., Mbayo K. A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS. Nature. 1988 Apr 21;332(6166):728–731. doi: 10.1038/332728a0. [DOI] [PubMed] [Google Scholar]

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