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ƒ^ƒCƒgƒ‹GIdentification of HIV-1-specific CD8+ T cell epitopes presented by HLA-A*2603
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AbstractG
Background
HIV-1-specific cytotoxic T lymphocyte (CTL) has a central role in suppression of HIV-1 replication in HIV-1-infected individuals. Therefore, identification of HIV-1 specific CTL epitopes is necessary for studies on immunopathogenesis of AIDS and vaccine development. HLA-A*26 is found in approximately 20% of Asian people who has three subtypes, A*2601, A*2602, and A*2603. Recently we identified HIV-1 epitopes presented by HLA-A*2601. We further extended our study to identification of HIV-1 epitopes presented by HLA-A*2603.

Methods
Sequences derived from HIV-1 SF2 were screened for HLA-A*26 binding motifs and 110 peptides were synthesized. We tested binding ability of these peptides by using HLA-stabilization assay with RMA-S-A*2603. PBMC from HIV-1-infected individuals with HLA-A*2603 were cultured for about 2 weeks after they were stimulated with HLA-A*2603-binding peptides. The cultured cells were tested for IFN-g production of CD8+ T cells by stimulating with C1R-A*2603 prepulsed with these peptides. We also investigated the ability of peptide-specific CD8+ T cells to produce IFN-g after stimulation with C1R-A*2603 cells infected with HIV-1 recombinant vaccinia virus.

Results
We selected 31 HLA-A*2603-binding peptides out of 110 HIV-1 peptides by using HLA-A*2603 stabilization assay. HLA-A*2603-binding Gag and Env peptides induced peptide-specific CD8+ T cells in PBMCs from 4 and 3 HIV-1-infected, HLA-A*2603+ individuals, respectively. These peptides-specific CD8+ T cells produced IFN-g after stimulation with C1R-A*2603 cells infected with HIV-1 recombinant vaccinia virus.

Conclusion
We have identified two epitopes presented by HLA-A*2603. Since the epitope derived from Gag is also presented by HLA-A*2601 and it is relatively conserved in HIV-1 subtype B, this epitope may be useful for vaccine development.


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E-mail: www@gtc.gtca.kumamoto-u.ac.jp