Murakoshi H, Akahoshi T, Koyanagi M, Chikata T, Naruto T, Maruyama R, Tamura Y, Ishizuka N, Gatanaga H, Oka S, Takiguchi M.
Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes. J Virol. 2015 May 15;89(10):5330-9.
- We identified 8 Gag and 5 Pol epitope-specific CD8+ T cells controlling HIV-1.
- These 13 CD8+ T cells synergistically control HIV-1 in vivo.
- HLA-B*52:01- and HLA-B*67:01-restricted CD8+ T cells play a predominant role in controlling HIV-1 in Japanese.
- Twelve out of these 13 epitopes were recognized as conserved or cross-recognized ones.
- These 12 epitopes are strong candidates of antigens for AIDS vaccines.
Identification and characterization of CD8+ T cells effectively controlling HIV-1 variants are necessary for the development of AIDS vaccines and the studies of AIDS pathogenesis although such CD8+ T cells have been only partially identified. We here sought to identify CD8+ T cells controlling HIV-1 variants in 401 Japanese individuals chronically infected with HIV-1 subtype B, in which protective alleles HLA-B*57 and HLA-B*27 are very rare, by using comprehensive and exhaustive methods. We identified 13 epitope-specific CD8+ T cells controlling HIV-1 in Japanese individuals though 9 of these epitopes were not previously reported. The breadth of the T cell responses to the 13 epitopes were inversely associated with plasma viral load (p = 2.2×10-11) and positively with CD4 counts (p = 1.2×10-11), indicating strong synergistic effects of these T cells on HIV-1 control in vivo. Nine of these epitopes were conserved among HIV-1 subtype B-infected individuals, whereas three out of 4 non-conserved epitopes were cross-recognized by the specific T cells. These findings indicate that these 12 epitopes are strong candidates of antigens for AIDS vaccine. The present study highlighted a strategy to identify CD8+ T cells controlling HIV-1 and demonstrated effective control of HIV-1 by those specific for 12 conserved or cross-reactive epitopes.