論文

査読有り
2015年5月

Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes

JOURNAL OF VIROLOGY
  • Hayato Murakoshi
  • Tomohiro Akahoshi
  • Madoka Koyanagi
  • Takayuki Chikata
  • Takuya Naruto
  • Rie Maruyama
  • Yoshiko Tamura
  • Naoki Ishizuka
  • Hiroyuki Gatanaga
  • Shinichi Oka
  • Masafumi Takiguchi
  • 全て表示

89
10
開始ページ
5330
終了ページ
5339
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1128/JVI.00020-15
出版者・発行元
AMER SOC MICROBIOLOGY

Identification and characterization of CD8(+) T cells effectively controlling HIV-1 variants are necessary for the development of AIDS vaccines and for studies of AIDS pathogenesis, although such CD8(+) T cells have been only partially identified. In this study, we 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 breadths of the T cell responses to the 13 epitopes were inversely associated with plasma viral load (P = 2.2 x 10(-11)) and positively associated with CD4 count (P = 1.2 x 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 four nonconserved epitopes were cross-recognized by the specific T cells. These findings indicate that these 12 epitopes are strong candidates for antigens for an 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.
IMPORTANCE
HLA-B*27-restricted and HLA-B*57-restricted cytotoxic T lymphocytes (CTLs) play a key role in controlling HIV-1 in Caucasians and Africans, whereas it is unclear which CTLs control HIV-1 in Asian countries, where HLA-B*57 and HLA-B*27 are very rare. A recent study showed that HLA-B*67:01 and HLA-B*52:01-C*12:02 haplotypes were protective alleles in Japanese individuals, but it is unknown whether CTLs restricted by these alleles control HIV-1. In this study, we identified 13 CTLs controlling HIV-1 in Japan by using comprehensive and exhaustive methods. They included 5 HLA-B*52:01-restricted and 3 HLA-B*67:01-restricted CTLs, suggesting that these CTLs play a predominant role in HIV-1 control. The 13 CTLs showed synergistic effects on HIV-1 control. Twelve out of these 13 epitopes were recognized as conserved or cross-recognized ones. These findings strongly suggest that these 12 epitopes are candidates for antigens for AIDS vaccines.

リンク情報
DOI
https://doi.org/10.1128/JVI.00020-15
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25741000
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000353329300014&DestApp=WOS_CPL
ID情報
  • DOI : 10.1128/JVI.00020-15
  • ISSN : 0022-538X
  • eISSN : 1098-5514
  • PubMed ID : 25741000
  • Web of Science ID : WOS:000353329300014

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