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HIV-1 control by conserved epitope-specific CTLs

May 15 2015

Masafumi Takiguchi

Paper Information

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.

Highlights

  • 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.

 

Abstract

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.

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