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
  • 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. [email protected].
  • 7. Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, VIC, 3010, Australia. [email protected].
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.