論文

査読有り
2012年12月

Differential Clade-Specific HLA-B*3501 Association with HIV-1 Disease Outcome Is Linked to Immunogenicity of a Single Gag Epitope

JOURNAL OF VIROLOGY
  • Philippa C. Matthews
  • ,
  • Madoka Koyanagi
  • ,
  • Henrik N. Kloverpris
  • ,
  • Mikkel Harndahl
  • ,
  • Anette Stryhn
  • ,
  • Tomohiro Akahoshi
  • ,
  • Hiroyuki Gatanaga
  • ,
  • Shinichi Oka
  • ,
  • Claudia Juarez Molina
  • ,
  • Humberto Valenzuela Ponce
  • ,
  • Santiago Avila Rios
  • ,
  • David Cole
  • ,
  • Jonathan Carlson
  • ,
  • Rebecca P. Payne
  • ,
  • Anthony Ogwu
  • ,
  • Alfred Bere
  • ,
  • Thumbi Ndung'u
  • ,
  • Kamini Gounder
  • ,
  • Fabian Chen
  • ,
  • Lynn Riddell
  • ,
  • Graz Luzzi
  • ,
  • Roger Shapiro
  • ,
  • Christian Brander
  • ,
  • Bruce Walker
  • ,
  • Andrew K. Sewell
  • ,
  • Gustavo Reyes Teran
  • ,
  • David Heckerman
  • ,
  • Eric Hunter
  • ,
  • Soren Buus
  • ,
  • Masafumi Takiguchi
  • ,
  • Philip J. R. Goulder

86
23
開始ページ
12643
終了ページ
12654
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1128/JVI.01381-12
出版者・発行元
AMER SOC MICROBIOLOGY

The strongest genetic influence on immune control in HIV-1 infection is the HLA class I genotype. Rapid disease progression in B-clade infection has been linked to HLA-B*35 expression, in particular to the less common HLA-B*3502 and HLA-B*3503 subtypes but also to the most prevalent subtype, HLA-B*3501. In these studies we first demonstrated that whereas HLA-B*3501 is associated with a high viral set point in two further B-clade-infected cohorts, in Japan and Mexico, this association does not hold in two large C-clade-infected African cohorts. We tested the hypothesis that clade-specific differences in HLA associations with disease outcomes may be related to distinct targeting of critical CD8(+) T-cell epitopes. We observed that only one epitope was significantly targeted differentially, namely, the Gag-specific epitope NPPIPVGDIY (NY10, Gag positions 253 to 262) (P = 2 x 10(-5)). In common with two other HLA-B*3501-restricted epitopes, in Gag and Nef, that were not targeted differentially, a response toward NY10 was associated with a significantly lower viral set point. Nonimmunogenicity of NY10 in B-clade-infected subjects derives from the Gag-D260E polymorphism present in similar to 90% of B-clade sequences, which critically reduces recognition of the Gag NY10 epitope. These data suggest that in spite of any inherent HLA-linked T-cell receptor repertoire differences that may exist, maximizing the breadth of the Gag-specific CD8(+) T-cell response, by the addition of even a single epitope, may be of overriding importance in achieving immune control of HIV infection. This distinction is of direct relevance to development of vaccines designed to optimize the anti-HIV CD8(+) T-cell response in all individuals, irrespective of HLA type.

Web of Science ® 被引用回数 : 31

リンク情報
DOI
https://doi.org/10.1128/JVI.01381-12
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22973023
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000310585300017&DestApp=WOS_CPL