Antagonism of cytotoxic T lymphocyte-mediated lysis by natural HIV-1 altered peptide ligands requires simultaneous presentation of agonist and antagonist peptides

Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135, Harcourt, Gillian C., Goulder, Philip J. R., Price, David ORCID: https://orcid.org/0000-0001-9416-2737 and Phillips, Rodney E. 1997. Antagonism of cytotoxic T lymphocyte-mediated lysis by natural HIV-1 altered peptide ligands requires simultaneous presentation of agonist and antagonist peptides. European Journal of Immunology 27 (9) , pp. 2323-2329. 10.1002/eji.1830270929

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Abstract

Mutations in human immunodeficiency virus (HIV) cluster in cytotoxic T lymphocyte (CTL) epitopes (Phillips, R. E. et al., Nature 1991. 354: 453) and are subject to immune-mediated positive selection (Price, D. A. et al., Proc. Natl. Acad. Sci. USA 1997. 94: 1890). We studied the effects of naturally occurring mutations in the HIV-1 p17 Gag HLA A2 restricted epitope SLYNTVATL on recognition by anti-HIV CTL. Most of these naturally occurring mutants escaped killing by one CTL line and the majority acted as CTL antagonists. We also investigated whether CTL exposed to a strict antagonist peptide restricted by HLA A2 were unresponsive when exposed to targets presenting the wild-type sequence. The results show that antagonism of anti-HIV CTL killing requires the simultaneous presence of agonist and antagonist peptide. We found no evidence that CTL exposed to an antagonist received a functionally negative signal since these CTL retained an unimpaired capacity to lyse targets bearing wild-type peptide.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Publisher:	John Wiley & Sons
ISSN:	0014-2980
Date of First Compliant Deposit:	16 June 2016
Date of Acceptance:	17 June 1997
Last Modified:	01 Nov 2022 10:32
URI:	https://orca.cardiff.ac.uk/id/eprint/91926

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