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Peptide-binding motifs associated with MHC molecules common in Chinese rhesus macaques are analogous to those of human HLA supertypes and include HLA-B27-like alleles
Authors:Bianca R Mothé  Scott Southwood  John Sidney  A Michelle English  Amanda Wriston  Ilka Hoof  Jeffrey Shabanowitz  Donald F Hunt  Alessandro Sette
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 Chemistry, University of Virginia, Charlottesville, VA, 22904, USA
4. Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, 2800, Lyngby, Denmark
5. The Bioinformatics Centre, Department of Biology and The Biotech Research and Innovation Centre, Copenhagen University, 2200, Copenhagen, Denmark
Abstract:Chinese rhesus macaques are of particular interest in simian immunodeficiency virus/human immunodeficiency virus (SIV/HIV) research as these animals have prolonged kinetics of disease progression to acquired immunodeficiency syndrome (AIDS), compared to their Indian counterparts, suggesting that they may be a better model for HIV. Nevertheless, the specific mechanism(s) accounting for these kinetics remains unclear. The study of major histocompatibility complex (MHC) molecules, including their MHC/peptide-binding motifs, provides valuable information for measuring cellular immune responses and deciphering outcomes of infection and vaccine efficacy. In this study, we have provided detailed characterization of six prevalent Chinese rhesus macaque MHC class I alleles, yielding a combined phenotypic frequency of 29 %. The peptide-binding specificity of two of these alleles, Mamu-A2*01:02 and Mamu-B*010:01, as well as the previously characterized allele Mamu-B*003:01 (and Indian rhesus Mamu-B*003:01), was found to be analogous to that of alleles in the HLA-B27 supertype family. Specific alleles in the HLA-B27 supertype family, including HLA-B*27:05, have been associated with long-term nonprogression to AIDS in humans. All six alleles characterized in the present study were found to have specificities analogous to HLA supertype alleles. These data contribute to the concept that Chinese rhesus macaque MHC immunogenetics is more similar to HLA than their Indian rhesus macaque counterparts and thereby warrants further studies to decipher the role of these alleles in the context of SIV infection.
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