2. Academic Validation
  3. Diverse MR1-restricted T cells in mice and humans

Diverse MR1-restricted T cells in mice and humans

  • Nat Commun. 2019 May 21;10(1):2243. doi: 10.1038/s41467-019-10198-w.
Hui-Fern Koay 1 2,  Nicholas A Gherardin 1 2,  Calvin Xu 1,  Rebecca Seneviratna 1 2,  Zhe Zhao 1,  Zhenjun Chen 1,  David P Fairlie 3 4,  James McCluskey 1,  Daniel G Pellicci 1 2 5,  Adam P Uldrich 1 2,  Dale I Godfrey 6 7
Affiliations

Affiliations

  • 1 Department of Microbiology & Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, 3000, Australia.
  • 2 Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, VIC, 3010, Australia.
  • 3 Division of Chemistry & Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
  • 4 Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Queensland, Brisbane, QLD, 4072, Australia.
  • 5 Murdoch Children's Research Institute, Parkville, VIC, 3052, Australia.
  • 6 Department of Microbiology & Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, 3000, Australia. godfrey@unimelb.edu.au.
  • 7 Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, VIC, 3010, Australia. godfrey@unimelb.edu.au.
PMID: 31113973 DOI: 10.1038/s41467-019-10198-w
Abstract

Mucosal-associated invariant T (MAIT) cells express an invariant TRAV1/TRAJ33 TCR-α chain and are restricted to the MHC-I-like molecule, MR1. Whether MAIT cell development depends on this invariant TCR-α chain is unclear. Here we generate Traj33-deficient mice and show that they are highly depleted of MAIT cells; however, a residual population remains and can respond to exogenous antigen in vitro or pulmonary Legionella challenge in vivo. These residual cells include some that express Trav1+ TCRs with conservative Traj-gene substitutions, and Others that express Trav1- TCRs with a broad range of Traj genes. We further report that human TRAV1-2- MR1-restricted T cells contain both MAIT-like and non-MAIT-like cells, as judged by their TCR repertoire, antigen reactivity and phenotypic features. These include a MAIT-like population that expresses a public, canonical TRAV36+ TRBV28+ TCR. Our findings highlight the TCR diversity and the resulting potential impact on antigen recognition by MR1-restricted T cells.

Figures