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.
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.
O'Connor
David H
DH
Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin, USA.
Mothe
Bianca R
BR
Weinfurter
Jason T
JT
Fuenger
Sarah
S
Rehrauer
William M
WM
Jing
Peicheng
P
Rudersdorf
Richard R
RR
Liebl
Max E
ME
Krebs
Kendall
K
Vasquez
Joshua
J
Dodds
Elizabeth
E
Loffredo
John
J
Martin
Sarah
S
McDermott
Adrian B
AB
Allen
Todd M
TM
Wang
Chenxi
C
Doxiadis
G G
GG
Montefiori
David C
DC
Hughes
Austin
A
Burton
Dennis R
DR
Allison
David B
DB
Wolinsky
Steven M
SM
Bontrop
Ronald
R
Picker
Louis J
LJ
Watkins
David I
DI
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*
D000939:Epitopes