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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.

Original publication




Journal article


Eur J Immunol

Publication Date





2323 - 2329


Antigen-Presenting Cells, Clonal Anergy, Cytotoxicity, Immunologic, Gene Products, gag, HIV Antigens, HIV Infections, HIV-1, HLA-A2 Antigen, Humans, Immunity, Cellular, Ligands, Peptides, Structure-Activity Relationship, T-Lymphocytes, Cytotoxic, Viral Proteins, gag Gene Products, Human Immunodeficiency Virus