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 - 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.
UR - http://www.scopus.com/inward/record.url?scp=85038589481&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038589481&partnerID=8YFLogxK
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 -