title: 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.
abstract: 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.
authors.affiliation: Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: Bianca R
authors.initials: BR
authors.lastname: Mothe
authors.forename: Jason T
authors.initials: JT
authors.lastname: Weinfurter
authors.forename: Sarah
authors.initials: S
authors.lastname: Fuenger
authors.forename: William M
authors.initials: WM
authors.lastname: Rehrauer
authors.forename: Peicheng
authors.initials: P
authors.lastname: Jing
authors.forename: Richard R
authors.initials: RR
authors.lastname: Rudersdorf
authors.forename: Max E
authors.initials: ME
authors.lastname: Liebl
authors.forename: Kendall
authors.initials: K
authors.lastname: Krebs
authors.forename: Joshua
authors.initials: J
authors.lastname: Vasquez
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dodds
authors.forename: John
authors.initials: J
authors.lastname: Loffredo
authors.forename: Sarah
authors.initials: S
authors.lastname: Martin
authors.forename: Adrian B
authors.initials: AB
authors.lastname: McDermott
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Chenxi
authors.initials: C
authors.lastname: Wang
authors.forename: G G
authors.initials: GG
authors.lastname: Doxiadis
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Austin
authors.initials: A
authors.lastname: Hughes
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Steven M
authors.initials: SM
authors.lastname: Wolinsky
authors.forename: Ronald
authors.initials: R
authors.lastname: Bontrop
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005805:Genes, MHC Class I; D008253:Macaca mulatta; D016133:Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology*
chemical_list: D000939:Epitopes