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

Autor: J M, Greene, P, Dash, S, Roy, C, McMurtrey, W, Awad, J S, Reed, K B, Hammond, S, Abdulhaqq, H L, Wu, B J, Burwitz, B F, Roth, D W, Morrow, J C, Ford, G, Xu, J Y, Bae, H, Crank, A W, Legasse, T H, Dang, H Y, Greenaway, M, Kurniawan, M C, Gold, M J, Harriff, D A, Lewinsohn, B S, Park, M K, Axthelm, J J, Stanton, S G, Hansen, L J, Picker, V, Venturi, W, Hildebrand, P G, Thomas, D M, Lewinsohn, E J, Adams, J B, Sacha
Rok vydání: 2016
Předmět:
Zdroj: Mucosal immunology
ISSN: 1935-3456
Popis: 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.
Databáze: OpenAIRE