TY - JOUR
T1 - The Role of MHC-E in T Cell immunity is conserved among humans, rhesus macaques, and cynomolgus macaques
AU - Wu, Helen L.
AU - Wiseman, Roger W.
AU - Hughes, Colette M.
AU - Webb, Gabriela M.
AU - Abdulhaqq, Shaheed A.
AU - Bimber, Benjamin N.
AU - Hammond, Katherine B.
AU - Reed, Jason S.
AU - Gao, Lina
AU - Burwitz, Benjamin J.
AU - Greene, Justin M.
AU - Ferrer, Fidel
AU - Legasse, Alfred W.
AU - Axthelm, Michael K.
AU - Park, Byung S.
AU - Brackenridge, Simon
AU - Maness, Nicholas J.
AU - McMichael, Andrew J.
AU - Picker, Louis J.
AU - O'Connor, David H.
AU - Hansen, Scott G.
AU - Sacha, Jonah B.
N1 - Funding Information:
and S.B. were funded by Bill & Melinda Gates Foundation Grant OPP1133649, Medical Research Council Grant K012037/1, and National Institute of Allergy and Infectious Disease Grant UM1 AI 00645.
Funding Information:
This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers R01AI117802 (awarded to J.B.S.), P01AI094417 (awarded to L.J.P.), F31AI12247 (awarded to H.L.W.), and P51OD011092 (awarded to the Oregon National Primate Research Center). A.J.M.
Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1700841
DO - 10.4049/jimmunol.1700841
M3 - Article
C2 - 29150562
AN - SCOPUS:85038589481
SN - 0022-1767
VL - 200
SP - 49
EP - 60
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -