Elsevier

Mucosal Immunology

Volume 10, Issue 3, May 2017, Pages 802-813
Mucosal Immunology

Article
MR1-restricted mucosal-associated invariant T (MAIT) cells respond to mycobacterial vaccination and infection in nonhuman primates

https://doi.org/10.1038/mi.2016.91Get rights and content
Under a Creative Commons license
open access

Abstract

Studies on mucosal-associated invariant T cells (MAITs) in nonhuman primates (NHP), a physiologically relevant model of human immunity, are handicapped due to a lack of macaque MAIT-specific reagents. Here we show that while MR1 ligand-contact residues are conserved between human and multiple NHP species, three T-cell receptor contact-residue mutations in NHP MR1 diminish binding of human MR1 tetramers to macaque MAITs. Construction of naturally loaded macaque MR1 tetramers facilitated identification and characterization of macaque MR1-binding ligands and MAITs, both of which mirrored their human counterparts. Using the macaque MR1 tetramer we show that NHP MAITs activated in vivo in response to both Bacillus Calmette-Guerin vaccination and Mycobacterium tuberculosis infection. These results demonstrate that NHP and human MR1 and MAITs function analogously, and establish a preclinical animal model to test MAIT-targeted vaccines and therapeutics for human infectious and autoimmune disease.

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Published online: 19 October 2016

Author contributions J.M.G. contributed to writing of the manuscript, performing experiments, analysis and figures. P.D. and C.M. contributed to performing experiments, analysis, writing, and figures. S.R. contributed to reagent development, writing, and figures. W.A., B.F.R., D.F.M., and M.C.G. contributed to performing experiments and analysis. J.S.R., S.A., H.L.W. B.J.B., J.C.F., and G.X. contributed to performing experiments. K.B.H., contributed to performing experiments, analysis, and figures. H.C., A.W.L., and M.K.A. contributed to coordinating experiments and animal care. T.H.D., H.G., M.K., M.J.H., M.C.G., and D.A.L. contributed to analysis and conception of experiments. B.S.P. contributed to statistical analysis of experiments. S.G.H. contributed to coordinating and performing experiments and their analysis. J.J.S. contributed to veterinary care and experimental advisement. L.J.P. contributed to conception of the experiments. V.V. contributed to analysis and writing. W.H. contributed to performing experiments and their analysis. P.G.T. contributed to conception of experiments and their analysis. D.M.L. contributed to conception of the experiments and their analysis. E.J.A. contributed to conception of the experiments, reagent development, analysis, and figure production. J.B.S contributed to conception of the experiments, performing the experiments, analysis, writing, and figure production.

Supplementary Material is linked to the online version of the paper

J M Greene, P Dash and S Roy: Co-first authors.