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

作者：Greene J M; Dash P; Roy S; McMurtrey C; Awad W; Reed J S; Hammond K B; Abdulha** S; Wu H L; Burwitz B J; Roth B F; Morrow D W; Ford J C; Xu G; Bae J Y; Crank H; Legasse A W; Dang T H; Greenaway H Y; Kurniawan M; Gold M C; Harriff M J; Lewinsohn D A; Park B S; Axthelm M K; Stanton J J; Hansen S G; Picker L J; Venturi V; Hildebrand W; Thomas P G; Lewinsohn D M; Adams E J; Sacha J B

来源：Mucosal Immunology, 2017, 10(3): 802-813.

DOI：10.1038/mi.2016.91

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.

• 出版日期2017-5