title: Functional analysis of frequently expressed Chinese rhesus macaque MHC class I molecules Mamu-A1*02601 and Mamu-B*08301 reveals HLA-A2 and HLA-A3 supertypic specificities.
abstract: The Simian immunodeficiency virus (SIV)-infected Indian rhesus macaque (Macaca mulatta) is the most established model of HIV infection and AIDS-related research, despite the potential that macaques of Chinese origin is a more relevant model. Ongoing efforts to further characterize the Chinese rhesus macaques' major histocompatibility complex (MHC) for composition and function should facilitate greater utilization of the species. Previous studies have demonstrated that Chinese-origin M. mulatta (Mamu) class I alleles are more polymorphic than their Indian counterparts, perhaps inferring a model more representative of human MHC, human leukocyte antigen (HLA). Furthermore, the Chinese rhesus macaque class I allele Mamu-A1*02201, the most frequent allele thus far identified, has recently been characterized and shown to be an HLA-B7 supertype analog, the most frequent supertype in human populations. In this study, we have characterized two additional alleles expressed with high frequency in Chinese rhesus macaques, Mamu-A1*02601 and Mamu-B*08301. Upon the development of MHC-peptide-binding assays and definition of their associated motifs, we reveal that these Mamu alleles share peptide-binding characteristics with the HLA-A2 and HLA-A3 supertypes, respectively, the next most frequent human supertypes after HLA-B7. These data suggest that Chinese rhesus macaques may indeed be a more representative model of HLA gene diversity and function as compared to the species of Indian origin and therefore a better model for investigating human immune responses.
authors.affiliation: Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Southwood
authors.forename: Christopher
authors.initials: C
authors.lastname: Solomon
authors.forename: Ilka
authors.initials: I
authors.lastname: Hoof
authors.forename: Richard
authors.initials: R
authors.lastname: Rudersdorf
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.forename: Angela
authors.initials: A
authors.lastname: Wahl
authors.forename: Oriana
authors.initials: O
authors.lastname: Hawkins
authors.forename: William
authors.initials: W
authors.lastname: Hildebrand
authors.forename: Bianca R
authors.initials: BR
authors.lastname: Mothé
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005787:Gene Frequency; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D015791:HLA-A3 Antigen / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; C092249:Mamu-B 01 antigen, Macaca mulatta