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MHC-E is a highly conserved nonclassical MHC class Ib molecule that predominantly binds and presents MHC class Ia leader sequence-derived peptides for NK cell regulation. However, MHC-E also binds pathogen-derived peptide Ags for presentation to CD8+ T cells. Given this role in adaptive immunity and its highly monomorphic nature in the human population, HLA-E is an attractive target for novel vaccine and immunotherapeutic modalities. Development of HLA-E-targeted therapies will require a physiologically relevant animal model that recapitulates HLA-E-restricted T cell biology. In this study, we investigated MHC-E immunobiology in two common nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM). Compared to humans and MCM, RM expressed a greater number of MHC-E alleles at both the population and individual level. Despite this difference, human, RM, and MCM MHC-E molecules were expressed at similar levels across immune cell subsets, equivalently upregulated by viral pathogens, and bound and presented identical peptides to CD8+ T cells. Indeed, SIV-specific, Mamu-E-restricted CD8+ T cells from RM recognized antigenic peptides presented by all MHC-E molecules tested, including cross-species recognition of human and MCM SIV-infected CD4+ T cells. Thus, MHC-E is functionally conserved among humans, RM, and MCM, and both RM and MCM represent physiologically relevant animal models of HLA-E-restricted T cell immunobiology.

Original publication

DOI

10.4049/jimmunol.1700841

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

18/12/2017

Volume

200

Pages

49 - 60

Addresses

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006.

Keywords

Killer Cells, Natural, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cells, Cultured, Animals, Macaca fascicularis, Macaca mulatta, Humans, Simian Acquired Immunodeficiency Syndrome, Peptides, Histocompatibility Antigens, Histocompatibility Antigens Class I, Antigens, Viral, Models, Animal, Antigen Presentation, Conserved Sequence, Simian immunodeficiency virus