AEGiS-07IAC: Mutation in T cell epitopes of HIV gag provides a mechanism for escape from immune control.

7th International AIDS Conference


Florence, Italy — June 16-21, 1991

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Mutation in T cell epitopes of HIV gag provides a mechanism for escape from immune control.

Int Conf AIDS 1991 Jun 16-21; 7:21 (abstract no. M.A.7)
Phillips R, Rowland-Jones S, Gotch F, Nixon DF, Ogunlesi A, Edwards J, McMichael AJ; Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK

OBJECTIVE: In longitudinal studies of HIV positive haemophiliacs, three distinct cytotoxic T cell (CTL) epitopes have been identified in Gag. To investigate the mechanism of fluctuation in CTL recognition of these epitopes and to search for escape mutants, we have determined the nucleotide sequence of HLA-B8 restricted Gag epitopes in serial peripheral blood samples. Synthetic peptides based on mutant sequences were then tested in CTL assays.

RESULTS: CTL from seropositive haemophiliacs recognised three distinct epitopes of the conserved Gag gene although the dominant epitope varied with time. There was no evidence of permanent loss of epitope recognition but sequence variation within epitopes defined by peptides 17-3 and 24-13 appeared during serial studies. Variant peptides based on these changes were usually recognised in CTL lysis assays. This study provides clear evidence that mutation occurs within conserved HIV CTL epitopes in vivo: accumulation of these variations could provide a mechanism for immune escape.

Keywords: AEGIS, Epitopes, T-Lymphocyte, T-Lymphocytes, Cytotoxic, HIV Infections, Epitopes, Genes, gag, HLA-B8 Antigen, Mutation, Variation (Genetics), HIV Seropositivity, Longitudinal Studies, genetics, ICA7KWDaegis,epitopes,t-lymphocyte,t-lymphocytes,cytotoxic,hivinfections,epitopes,genes,gag,hla-b8antigen,mutation,variation(genetics),hivseropositivity,longitudinalstudies,genetics,ica7
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MA7

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