Cytotoxic T lymphocytes recognize structurally diverse, clade-specific andcross-reactive peptides in human immunodeficiency virus type-1 gag throughHLA-B53

Human immunodeficiency virus type-1 (HIV-1) cytotoxic T lymphocyte (CTL) ep itopes have largely been defined in Caucasian populations infected with cla de B virus. identification of potentially protective CTL epitopes in non-B clade-infected African subjects is important for vaccine development. In a study of CTL responses in clade A-infected Gambians, using cytotoxicity, in terferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISpot) and HLA-B53-p eptide tetramer assays, we identified three HLA-B53-restricted epitopes in HIV-1 gag p24. CTL specific for an epitope in a highly immunogenic region o f the p24 protein showed no cross-reactivity to other HIV-1 clades. Two of the epitopes would not have been predicted from the peptide-binding motif d ue to the absence of a proline anchor at position 2. Structural analysis of HLA-B53 and its relative, HLA B35, enabled us to re-define the peptide-bin ding motif to include other P2 anchors. These results demonstrate the value of combined immunological and structural analyses in defining novel CTL ep itopes and have implications for HIV-1 vaccine design.