論文

査読有り
2011年1月

Selection of escape mutant by HLA-C-restricted HIV-1 Pol-specific cytotoxic T lymphocytes carrying strong ability to suppress HIV-1 replication

EUROPEAN JOURNAL OF IMMUNOLOGY
  • Kazutaka Honda
  • ,
  • Nan Zheng
  • ,
  • Hayato Murakoshi
  • ,
  • Masao Hashimoto
  • ,
  • Keiko Sakai
  • ,
  • Mohamed Ali Borghan
  • ,
  • Takayuki Chikata
  • ,
  • Madoka Koyanagi
  • ,
  • Yoshiko Tamura
  • ,
  • Hiroyuki Gatanaga
  • ,
  • Shinichi Oka
  • ,
  • Masafumi Takiguchi

41
1
開始ページ
97
終了ページ
106
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/eji.201040841
出版者・発行元
WILEY-BLACKWELL PUBLISHING, INC

HIV-1 mutants escaping from HLA-A-or HLA-B-restricted CTL have been well studied, but those from HLA-C-restricted CTL have not. Therefore we investigated the ability of HLA-C-restricted CTL to select HIV-1 escape mutants. In the present study, we identified two novel HLA-Cw*1202-restricted Pol-specific CTL epitopes (Pol328-9 and Pol463-10). CTL specific for these epitopes were detected in 25-40% of chronically HIV-1-infected HLA-Cw*1202(+) 1 individuals and had strong abilities to kill HIV-1-infected cells and to suppress HIV-1 replication in vitro, suggesting that these CTL may have the ability to effectively control HIV-1 in some HLA-Cw*1202(+) individuals. Sequence analysis of these epitopes showed that a V-to-A substitution at the 9th position (V9A) of Pol 463-10 was significantly associated with the HLA-Cw*1202 allele and that the V9A mutant was slowly selected in the HLA-Cw*1202(+) individuals. Pol 463-10-specific CTL failed both to kill the V9A virus-infected cells and to suppress replication of the V9A mutant. These results indicate that the V9A mutation was selected as an escape mutant by the Pol463-10-specific CTL. The present study strongly suggests that some HLA-C-restricted CTL have a strong ability to suppress HIV-1 replication so that they can select HIV escape mutants as in the case of HLA-A-restricted or HLA-B-restricted CTL.

Web of Science ® 被引用回数 : 18

リンク情報
DOI
https://doi.org/10.1002/eji.201040841
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/21182081
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000285933000011&DestApp=WOS_CPL