title: 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.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Vic., Australia.
authors.forename: Miranda Z
authors.initials: MZ
authors.lastname: Smith
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fernandez
authors.forename: Amy
authors.initials: A
authors.lastname: Chung
authors.forename: C Jane
authors.initials: CJ
authors.lastname: Dale
authors.forename: Robert
authors.initials: R
authors.lastname: De Rose
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Kendall C
authors.initials: KC
authors.lastname: Krebs
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: 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*
chemical_list: D017931:DNA Primers; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D016056:Immunodominant Epitopes