September 22, 2019  |  

The role of MHC-E in T cell immunity is conserved among humans, rhesus macaques, and cynomolgus macaques.

Authors: Wu, Helen L and Wiseman, Roger W and Hughes, Colette M and Webb, Gabriela M and Abdulhaqq, Shaheed A and Bimber, Benjamin N and Hammond, Katherine B and Reed, Jason S and Gao, Lina and Burwitz, Benjamin J and Greene, Justin M and Ferrer, Fidel and Legasse, Alfred W and Axthelm, Michael K and Park, Byung S and Brackenridge, Simon and Maness, Nicholas J and McMichael, Andrew J and Picker, Louis J and O'Connor, David H and Hansen, Scott G and Sacha, Jonah B

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. Copyright © 2017 by The American Association of Immunologists, Inc.

Journal: Journal of immunology
DOI: 10.4049/jimmunol.1700841
Year: 2018

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