Abstract
A human leukocyte antigen A24-restricted CD8+ cytotoxic T-cell clone specific for gp41 of human immunodeficiency virus type 1 was isolated from an infected individual. The epitope was localized to amino acids 584 to 591 (YLKDQQLL, NL43 env sequence) of gp41 by using a panel of recombinant vaccinia viruses that contain truncated env genes and synthetic peptides. The clone killed autologous B-lymphoblastoid cell lines pulsed with a synthetic peptide reflecting the sequence of the IIIB and MN strains. This clone, however, failed to kill target cells pulsed with the peptides that have a mutation from Lys to Arg or Gln at amino acid 585 which is present in some prototype human immunodeficiency virus type 1 strains, e.g., ADA, JFL, SC, ALA1, BAL1, SF2, VRF, SF33, and WMJ2. This finding that a mutation at amino acid 585 on gp41 results in nonrecognition by human leukocyte antigen A24-restricted CD8+ cytotoxic T lymphocytes suggests that antigenic variation at T-cell epitopes contributes to the failure of immune control of human immunodeficiency virus type 1 infections.
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- 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]
- Earl P. L., Koenig S., Moss B. Biological and immunological properties of human immunodeficiency virus type 1 envelope glycoprotein: analysis of proteins with truncations and deletions expressed by recombinant vaccinia viruses. J Virol. 1991 Jan;65(1):31–41. doi: 10.1128/jvi.65.1.31-41.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Klavinskis L. S., Tishon A., Oldstone M. B. Efficiency and effectiveness of cloned virus-specific cytotoxic T lymphocytes in vivo. J Immunol. 1989 Sep 15;143(6):2013–2016. [PubMed] [Google Scholar]
- Koenig S., Fuerst T. R., Wood L. V., Woods R. M., Suzich J. A., Jones G. M., de la Cruz V. F., Davey R. T., Jr, Venkatesan S., Moss B. Mapping the fine specificity of a cytolytic T cell response to HIV-1 nef protein. J Immunol. 1990 Jul 1;145(1):127–135. [PubMed] [Google Scholar]
- Littaua R. A., Oldstone M. B., Takeda A., Debouck C., Wong J. T., Tuazon C. U., Moss B., Kievits F., Ennis F. A. An HLA-C-restricted CD8+ cytotoxic T-lymphocyte clone recognizes a highly conserved epitope on human immunodeficiency virus type 1 gag. J Virol. 1991 Aug;65(8):4051–4056. doi: 10.1128/jvi.65.8.4051-4056.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Littaua R. A., Oldstone M. B., Takeda A., Ennis F. A. A CD4+ cytotoxic T-lymphocyte clone to a conserved epitope on human immunodeficiency virus type 1 p24: cytotoxic activity and secretion of interleukin-2 and interleukin-6. J Virol. 1992 Jan;66(1):608–611. doi: 10.1128/jvi.66.1.608-611.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lukacher A. E., Braciale V. L., Braciale T. J. In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific. J Exp Med. 1984 Sep 1;160(3):814–826. doi: 10.1084/jem.160.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nixon D. F., Townsend A. R., Elvin J. G., Rizza C. R., Gallwey J., McMichael A. J. HIV-1 gag-specific cytotoxic T lymphocytes defined with recombinant vaccinia virus and synthetic peptides. Nature. 1988 Dec 1;336(6198):484–487. doi: 10.1038/336484a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Plata F., Autran B., Martins L. P., Wain-Hobson S., Raphaël M., Mayaud C., Denis M., Guillon J. M., Debré P. AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature. 1987 Jul 23;328(6128):348–351. doi: 10.1038/328348a0. [DOI] [PubMed] [Google Scholar]
- Sethi K. K., Näher H., Stroehmann I. Phenotypic heterogeneity of cerebrospinal fluid-derived HIV-specific and HLA-restricted cytotoxic T-cell clones. Nature. 1988 Sep 8;335(6186):178–181. doi: 10.1038/335178a0. [DOI] [PubMed] [Google Scholar]
- Siliciano R. F., Lawton T., Knall C., Karr R. W., Berman P., Gregory T., Reinherz E. L. 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. 1988 Aug 12;54(4):561–575. doi: 10.1016/0092-8674(88)90078-5. [DOI] [PubMed] [Google Scholar]
- 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]
- Takahashi K., Dai L. C., Fuerst T. R., Biddison W. E., Earl P. L., Moss B., Ennis F. A. Specific lysis of human immunodeficiency virus type 1-infected cells by a HLA-A3.1-restricted CD8+ cytotoxic T-lymphocyte clone that recognizes a conserved peptide sequence within the gp41 subunit of the envelope protein. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10277–10281. doi: 10.1073/pnas.88.22.10277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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. HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature. 1987 Jul 23;328(6128):345–348. doi: 10.1038/328345a0. [DOI] [PubMed] [Google Scholar]
- Walker B. D., Flexner C., Birch-Limberger K., Fisher L., Paradis T. J., Aldovini A., Young R., Moss B., Schooley R. T. Long-term culture and fine specificity of human cytotoxic T-lymphocyte clones reactive with human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9514–9518. doi: 10.1073/pnas.86.23.9514. [DOI] [PMC free article] [PubMed] [Google Scholar]