論文

査読有り
2014年5月

HIV Subtype Influences HLA- B*07: 02-Associated HIV Disease Outcome

AIDS RESEARCH AND HUMAN RETROVIRUSES
  • Henrik N. Kloverpris
  • ,
  • Emily Adland
  • ,
  • Madoka Koyanagi
  • ,
  • Anette Stryhn
  • ,
  • Mikkel Harndahl
  • ,
  • Philippa C. Matthews
  • ,
  • Roger Shapiro
  • ,
  • Bruce D. Walker
  • ,
  • Thumbi Ndung'u
  • ,
  • Christian Brander
  • ,
  • Masafumi Takiguchi
  • ,
  • Soren Buus
  • ,
  • Philip Goulder

30
5
開始ページ
468
終了ページ
475
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1089/aid.2013.0197
出版者・発行元
MARY ANN LIEBERT, INC

Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid disease progression. HLA-B*07:02 is an HLA class I molecule that is prevalent in most populations worldwide and that has previously been consistently linked to accelerated disease progression in B-clade infection. This study investigates the observation that HLA-B*07:02 is not associated with a high viral setpoint in C-clade infection. We examine the hypothesis that this clade-specific difference in association with disease outcome may be related to distinct targeting of CD8(+) T cell epitopes. We observed that C-clade-infected individuals with HLA-B*07:02 target a broader range of Gag epitopes, and to higher magnitudes, than do individuals infected with B-clade infection. In particular, a novel p17-Gag (Gag22-30, RPGGKKHYM) epitope is targeted in >50% of HLA-B*07:02-positive C-clade-infected individuals but clade-specific differences in this epitope result in nonimmunogenicity in B-clade infection. Only the C-clade p24-Gag GL9 (Gag355-363, GPSHKARVL) epitope-specific CD8(+) T cell response out of 16 studied was associated with a low viral setpoint. Although this epitope was also targeted in B-clade infection, the escape mutant S357S is present at higher frequency in B-clade infection than in C-clade infection (70% versus 43% in HLA-B*07:02-negative subjects). These data support earlier studies suggesting that increased breadth of the Gag-specific CD8(+) T cell response may contribute to improved HIV immune control irrespective of the particular HLA molecules expressed.

Web of Science ® 被引用回数 : 12

リンク情報
DOI
https://doi.org/10.1089/aid.2013.0197
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/24010680
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000335661900010&DestApp=WOS_CPL