Journal article

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, Dale I Godfrey

Nature Communications | Nature Research (part of Springer Nature) | Published : 2019

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 a..

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Grants

Awarded by Department of Education and Training | Australian Research Council (ARC)


Awarded by Department of Health | National Health and Medical Research Council (NHMRC)


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (NHMRC; 1063587, 1083942, 1113293, 1140126) and the Australian Research Council (ARC; CE140100011). H.-F.K. is supported by an NHMRC ECF fellowship (1160333); D.G.P. is supported by an NHMRC CDF fellowship (1144308); A.P.U. is supported by an ARC Future Fellowship (FT140100278); D.F. and D.I.G. are supported by NHMRC Senior Principal Research Fellowships (1117017 and 1117766, respectively). The authors thank Dr Marco Herold and Dr Andrew Kueh from Walter and Eliza Hall Institute and in association with the Australian Phenomics Network for generating and providing Traj33 gene-deleted heterozygous mice; Zheng Ruan, Scott Reddiex, Marcin Ciula and Catarina Almeida for technical assistance and David Taylor, Kelsey Endler and the staff in the Doherty Institute Animal House for animal husbandry assistance. We also thank Tina Luke and staff at the Doherty Institute Flow Cytometry Facility and Vanta Jameson and staff at the Melbourne Brain Centre Flow Cytometry Facility for flow cytometry support.