Human leukocyte antigen (
HLA)-A*26 is one of the alleles associated with a slow progression to
AIDS. Identification and characterization of HIV-1-specific
epitopes presented by this allele are necessary for studies on the immunopathogenesis of
AIDS and
vaccine development in Asia, where three
HLA-A*26 subtypes are frequently found. In the present study, we sought to identify
HLA-A*2603-restricted HIV-1
epitopes by using reverse immunogenetics and to compare them with
HLA-A*2601-restricted ones recently identified. We found that 31 of 110 HIV-1
peptides bound to
HLA-A*2603 and that only two
peptides (Gag169-177 and Env63-72) induced specific CD8+T cells by stimulating peripheral blood mononuclear leukocytes from HIV-1-infected individuals carrying
HLA-A*2603. The specific cytotoxic T lymphocyte clones killed HIV-1 recombinant
vaccinia-infected cells, indicating that these two
peptides were naturally occurring
peptides presented by
HLA-A*2603. Gag169-177-specific CD8+T cells were frequently detected in both
HLA-A*2601+ and -A*2603+ individuals with chronic HIV-1
infection, whereas Env63-72-specific ones were frequently detected only in the
HLA-A*2603+ individuals. Gag169-177
peptide bound equally to both
HLA-A*26
antigens, whereas Env63-72
peptide bound to A*2603 much more strongly than to A*2601. These findings suggest that the relative affinity of these
peptides for the
HLA-A*26 subtypes determines whether these
peptides are recognized as
epitopes in HIV-1-infected individuals carrying these alleles.