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The Role of MHC-E in T Cell Immunity Is Conserved among Humans, Rhesus Macaques, and Cynomolgus Macaques.

Authors
  • Wu, Helen L1
  • Wiseman, Roger W2
  • Hughes, Colette M1
  • Webb, Gabriela M1
  • Abdulhaqq, Shaheed A1
  • Bimber, Benjamin N3
  • Hammond, Katherine B1
  • Reed, Jason S1
  • Gao, Lina3, 4
  • Burwitz, Benjamin J1, 3
  • Greene, Justin M1
  • Ferrer, Fidel1
  • Legasse, Alfred W3
  • Axthelm, Michael K3
  • Park, Byung S3, 5
  • Brackenridge, Simon6
  • Maness, Nicholas J7, 8
  • McMichael, Andrew J6
  • Picker, Louis J1, 3
  • O'Connor, David H2, 9
  • And 2 more
  • 1 Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006.
  • 2 Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706.
  • 3 Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006.
  • 4 Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239.
  • 5 School of Public Health, Oregon Health and Science University, Portland, OR 97239.
  • 6 Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 2JD, United Kingdom. , (United Kingdom)
  • 7 Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433.
  • 8 Department of Microbiology and Immunology, School of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70118; and.
  • 9 Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715.
  • 10 Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006; [email protected]
Type
Published Article
Journal
The Journal of Immunology
Publisher
The American Association of Immunologists
Publication Date
Jan 01, 2018
Volume
200
Issue
1
Pages
49–60
Identifiers
DOI: 10.4049/jimmunol.1700841
PMID: 29150562
Source
Medline
License
Unknown

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 HLA-E-restricted T cell immunobiology.

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