The pigtail macaque MHC class I allele Mane-A*10 presents an immundominant SIV Gag epitope: identification, tetramer development and implications of immune escape and reversion.
The pigtail macaque (Macaca nemestrina) is a common model for the study of AIDS. The pigtail major histocompatibility complex class I allele Mane-A*10 restricts an immunodominant simian immunodeficiency virus (SIV) Gag epitope (KP9) which rapidly mutates to escape T cell recognition following acute simian/human immunodeficiency virus infection. Two technologies for the detection of Mane-A*10 in outbred pigtail macaques were developed: reference strand-mediated conformational analysis and sequence-specific primer polymerase chain reaction. A Mane-A*10/KP9 tetramer was then developed to quantify CD8(+) T lymphocytes primed by multigenic DNA vaccination, which have previously been difficult to detect using standard interferon-gamma-based T cell assays. We also demonstrate mutational escape at KP9 following acute SIV infection. Mane-A*10(+) animals have lower set point SIV levels than Mane-A*10(-) animals, suggesting a significant fitness cost of escape. These studies pave the way for a more robust understanding of HIV vaccines in pigtail macaques.
Smith
Miranda Z
MZ
Department of Microbiology and Immunology, University of Melbourne, Parkville, Vic., Australia.
Fernandez
Caroline S
CS
Chung
Amy
A
Dale
C Jane
CJ
De Rose
Robert
R
Lin
Jie
J
Brooks
Andrew G
AG
Krebs
Kendall C
KC
Watkins
David I
DI
O'Connor
David H
DH
Davenport
Miles P
MP
Kent
Stephen J
SJ
D000483:Alleles; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers; D019143:Evolution, Molecular; D005434:Flow Cytometry / Q000379:methods / Q000662:veterinary; D015683:Gene Products, gag / Q000235:genetics; D005805:Genes, MHC Class I / Q000235:genetics*; D020180:Heteroduplex Analysis; D016056:Immunodominant Epitopes / Q000235:genetics; D008254:Macaca nemestrina; D008992:Monkey Diseases / Q000276:immunology* / Q000821:virology*; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods / Q000662:veterinary; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D017931:DNA Primers; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D016056:Immunodominant Epitopes