title: Analysis of pigtail macaque major histocompatibility complex class I molecules presenting immunodominant simian immunodeficiency virus epitopes.
abstract: Successful human immunodeficiency virus (HIV) vaccines will need to induce effective T-cell immunity. We studied immunodominant simian immunodeficiency virus (SIV) Gag-specific T-cell responses and their restricting major histocompatibility complex (MHC) class I alleles in pigtail macaques (Macaca nemestrina), an increasingly common primate model for the study of HIV infection of humans. CD8+ T-cell responses to an SIV epitope, Gag164-172KP9, were present in at least 15 of 36 outbred pigtail macaques. The immunodominant KP9-specific response accounted for the majority (mean, 63%) of the SIV Gag response. Sequencing from six macaques identified 7 new Mane-A and 13 new Mane-B MHC class I alleles. One new allele, Mane-A*10, was common to four macaques that responded to the KP9 epitope. We adapted reference strand-mediated conformational analysis (RSCA) to MHC class I genotype M. nemestrina. Mane-A*10 was detected in macaques presenting KP9 studied by RSCA but was absent from non-KP9-presenting macaques. Expressed on class I-deficient cells, Mane-A*10, but not other pigtail macaque MHC class I molecules, efficiently presented KP9 to responder T cells, confirming that Mane-A*10 restricts the KP9 epitope. Importantly, naive pigtail macaques infected with SIVmac251 that respond to KP9 had significantly reduced plasma SIV viral levels (log10 0.87 copies/ml; P=0.025) compared to those of macaques not responding to KP9. The identification of this common M. nemestrina MHC class I allele restricting a functionally important immunodominant SIV Gag epitope establishes a basis for studying CD8+ T-cell responses against AIDS in an important, widely available nonhuman primate species.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Miranda Z
authors.initials: MZ
authors.lastname: Smith
authors.forename: C Jane
authors.initials: CJ
authors.lastname: Dale
authors.forename: Robert
authors.initials: R
authors.lastname: De Rose
authors.forename: Ivan
authors.initials: I
authors.lastname: Stratov
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fernandez
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Jason
authors.initials: J
authors.lastname: Weinfurter
authors.forename: Kendall
authors.initials: K
authors.lastname: Krebs
authors.forename: Cara
authors.initials: C
authors.lastname: Riek
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
authors.forename: David H
authors.initials: DH
authors.lastname: O'connor
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag / Q000276:immunology; D005805:Genes, MHC Class I; D016056:Immunodominant Epitopes; D007371:Interferon-gamma / Q000096:biosynthesis; D008254:Macaca nemestrina / Q000276:immunology*; D008969:Molecular Sequence Data; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D016056:Immunodominant Epitopes; D007371:Interferon-gamma