Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses.

Published

Journal Article

Certain major histocompatibility complex class I (MHC-I) alleles are associated with delayed disease progression in individuals infected with human immunodeficiency virus (HIV) and in macaques infected with simian immunodeficiency virus (SIV). However, little is known about the influence of these MHC alleles on acute-phase cellular immune responses. Here we follow 51 animals infected with SIV(mac)239 and demonstrate a dramatic association between Mamu-A*01 and -B*17 expression and slowed disease progression. We show that the dominant acute-phase cytotoxic T lymphocyte (CTL) responses in animals expressing these alleles are largely directed against two epitopes restricted by Mamu-A*01 and one epitope restricted by Mamu-B*17. One Mamu-A*01-restricted response (Tat(28-35)SL8) and the Mamu-B*17-restricted response (Nef(165-173)IW9) typically select for viral escape variants in early SIV(mac)239 infection. Interestingly, animals expressing Mamu-A*1 and -B*17 have less variation in the Tat(28-35)SL8 epitope during chronic infection than animals that express only Mamu-A*01. Our results show that MHC-I alleles that are associated with slow progression to AIDS bind epitopes recognized by dominant CTL responses during acute infection and underscore the importance of understanding CTL responses during primary HIV infection.

Full Text

Duke Authors

Cited Authors

  • O'Connor, DH; Mothe, BR; Weinfurter, JT; Fuenger, S; Rehrauer, WM; Jing, P; Rudersdorf, RR; Liebl, ME; Krebs, K; Vasquez, J; Dodds, E; Loffredo, J; Martin, S; McDermott, AB; Allen, TM; Wang, C; Doxiadis, GG; Montefiori, DC; Hughes, A; Burton, DR; Allison, DB; Wolinsky, SM; Bontrop, R; Picker, LJ; Watkins, DI

Published Date

  • August 2003

Published In

Volume / Issue

  • 77 / 16

Start / End Page

  • 9029 - 9040

PubMed ID

  • 12885919

Pubmed Central ID

  • 12885919

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.77.16.9029-9040.2003

Language

  • eng

Conference Location

  • United States