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

J. M. Greene, P. Dash, S. Roy, C. McMurtrey, W. Awad, J. S. Reed, K. B. Hammond, S. Abdulhaqq, H. L. Wu, Benjamin Burwitz, B. F. Roth, D. W. Morrow, J. C. Ford, Guangwu Xu, J. Y. Bae, H. Crank, A. W. Legasse, T. H. Dang, H. Y. Greenaway, M. KurniawanMarielle Gold, Melanie Harriff, Deborah Lewinsohn, Byung Park, Michael Axthelm, Jeffrey Stanton, Scott Hansen, Louis Picker, V. Venturi, W. Hildebrand, P. G. Thomas, David Lewinsohn, E. J. Adams, Jonah Sacha

Research output: Contribution to journalArticle

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)802-813
Number of pages12
JournalMucosal Immunology
Volume10
Issue number3
DOIs
StatePublished - May 1 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'MR1-restricted mucosal-associated invariant T (MAIT) cells respond to mycobacterial vaccination and infection in nonhuman primates'. Together they form a unique fingerprint.

  • Cite this

    Greene, J. M., Dash, P., Roy, S., McMurtrey, C., Awad, W., Reed, J. S., Hammond, K. B., Abdulhaqq, S., Wu, H. L., Burwitz, B., 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., ... Sacha, J. (2017). MR1-restricted mucosal-associated invariant T (MAIT) cells respond to mycobacterial vaccination and infection in nonhuman primates. Mucosal Immunology, 10(3), 802-813. https://doi.org/10.1038/mi.2016.91