Diverse MR1-restricted T cells in mice and humans

Hui-Fern Koay, Nicholas A. Gherardin, Calvin Xu, Rebecca Seneviratna, Zhe Zhao, Zhenjun Chen, David P. Fairlie, James McCluskey, Daniel G. Pellicci, Adam P. Uldrich and Dale I. Godfrey ()
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Hui-Fern Koay: University of Melbourne
Nicholas A. Gherardin: University of Melbourne
Calvin Xu: University of Melbourne
Rebecca Seneviratna: University of Melbourne
Zhe Zhao: University of Melbourne
Zhenjun Chen: University of Melbourne
David P. Fairlie: The University of Queensland
James McCluskey: University of Melbourne
Daniel G. Pellicci: University of Melbourne
Adam P. Uldrich: University of Melbourne
Dale I. Godfrey: University of Melbourne

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10198-w

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