The Role of MHC-E in T Cell immunity is conserved among humans, rhesus macaques, and cynomolgus macaques

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

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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 HLAE-restricted T cell immunobiology.

Original languageEnglish (US)
Pages (from-to)49-60
Number of pages12
JournalJournal of Immunology
Volume200
Issue number1
DOIs
StatePublished - Jan 1 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Wu, H. L., Wiseman, R. W., Hughes, C. M., Webb, G. M., Abdulhaqq, S. A., Bimber, B. N., Hammond, K. B., Reed, J. S., Gao, L., Burwitz, B. J., Greene, J. M., Ferrer, F., Legasse, A. W., Axthelm, M. K., Park, B. S., Brackenridge, S., Maness, N. J., McMichael, A. J., Picker, L. J., ... Sacha, J. B. (2018). The Role of MHC-E in T Cell immunity is conserved among humans, rhesus macaques, and cynomolgus macaques. Journal of Immunology, 200(1), 49-60. https://doi.org/10.4049/jimmunol.1700841