Identification and characterization of HIV-1 epitopes presented by HLA-A*2603: comparison between HIV-1 epitopes presented by A*2601 and A*2603.
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.
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
Yuka
Y
Kawashima
Manami
M
Satoh
Shinichi
S
Oka
Masafumi
M
Takiguchi
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology* / Q000378:metabolism*; D015789:HLA-A2 Antigen / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism
D000939:Epitopes; D015234:HLA-A Antigens; C039683:HLA-A*26 antigen; C541137:HLA-A*26:01 antigen; C541138:HLA-A*26:03 antigen; D015789:HLA-A2 Antigen; D010455:Peptides; D014764:Viral Proteins