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

Scott Southwood, Christopher Solomon, Ilka Hoof, Richard Rudersdorf, John Sidney, Bjoern Peters, Angela Wahl, Oriana Hawkins, William Hildebrand, Bianca R. Mothé, Alessandro Sette

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    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.
    Original languageEnglish
    JournalImmunogenetics
    Volume63
    Issue number5
    Pages (from-to)275-290
    ISSN0093-7711
    DOIs
    Publication statusPublished - 2011

    Bibliographical note

    This article is published with open access at Springerlink.com. The online version of this article (doi:10.1007/s00251-010-0502-8) contains supplementary material, which is available to authorized users.

    Keywords

    • Rhesus macaque
    • HLA supertype
    • Peptide-binding motif
    • MHC

    Cite this

    Southwood, S., Solomon, C., Hoof, I., Rudersdorf, R., Sidney, J., Peters, B., Wahl, A., Hawkins, O., Hildebrand, W., Mothé, B. R., & Sette, A. (2011). 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. Immunogenetics, 63(5), 275-290. https://doi.org/10.1007/s00251-010-0502-8