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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
Authors:Southwood Scott  Solomon Christopher  Hoof Ilka  Rudersdorf Richard  Sidney John  Peters Bjoern  Wahl Angela  Hawkins Oriana  Hildebrand William  Mothé Bianca R  Sette Alessandro
Institution:1. Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA
2. Department of Biological Sciences, California State University??San Marcos, San Marcos, CA, 92096, USA
3. Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, 2800, Lyngby, Denmark
4. Department of Pathology and Laboratory Medicine, University of Wisconsin??Madison, Madison, WI, 53706, USA
5. Department of Microbiology and Immunology, The University of Oklahoma, Oklahoma City, OK, 73104, USA
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?Cpeptide-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.
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