Diversity of T Cells Restricted by the MHC Class I-Related Molecule MR1 Facilitates Differential Antigen Recognition

NA Gherardin; AN Keller; RE Woolley; J Le Nours; DS Ritchie; PJ Neeson; RW Birkinshaw; SBG Eckle; JN Waddington; L Liu; DP Fairlie; AP Uldrich; DG Pellicci; J McCluskey; DI Godfrey; J Rossjohn

Journal article

Diversity of T Cells Restricted by the MHC Class I-Related Molecule MR1 Facilitates Differential Antigen Recognition

NA Gherardin, AN Keller, RE Woolley, J Le Nours, DS Ritchie, PJ Neeson, RW Birkinshaw, SBG Eckle, JN Waddington, L Liu, DP Fairlie, AP Uldrich, DG Pellicci, J McCluskey, DI Godfrey, J Rossjohn

Immunity | CELL PRESS | Published : 2016

DOI: 10.1016/j.immuni.2015.12.005

Abstract

A characteristic of mucosal-associated invariant T (MAIT) cells is the expression of TRAV1-2+ T cell receptors (TCRs) that are activated by riboflavin metabolite-based antigens (Ag) presented by the MHC-I related molecule, MR1. Whether the MR1-restricted T cell repertoire and associated Ag responsiveness extends beyond these cells remains unclear. Here, we describe MR1 autoreactivity and folate-derivative reactivity in a discrete subset of TRAV1-2+ MAIT cells. This recognition was attributable to CDR3β loop-mediated effects within a consensus TRAV1-2+ TCR-MR1-Ag footprint. Furthermore, we have demonstrated differential folate- and riboflavin-derivative reactivity by a diverse population of "..

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University of Melbourne Researchers

Nicholas Gherardin Author

David Ritchie Author

Sidonia Eckle Author

Adam Uldrich Author

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Awarded by National Health and Medical Research Council

Funding Acknowledgements

We thank Marcin Ciula and Bronwyn Meehan for technical assistance and advice. We thank the Monash Macromolecular Crystallization Facility for support and the Australian Synchrotron staff for assistance with data collection. We thank staff from the Flow Cytometry facility at The University of Melbourne and Melbourne Brain Centre. We are grateful to Dr. Dario Vignali (St. Jude Children's research hospital) and Professor Stephen Turner (The University of Melbourne) for providing pMIG expression vector and Dr. Paul Savage (Brigham Young University) for alpha- GalCer analog PBS-44. This work was supported by the National Health and Medical Research Council of Australia ((NHMRC) 1013667 and 1063587) and the Australian Research Council (ARC; CE140100011 and LE110100106). N.A.G. is supported by a Leukaemia Foundation of Australia Postgraduate Scholarship; A.P.U. is supported by an ARC Future Fellowship; D.G.P. is supported by an NHMRC ECF Fellowship (1054431); J.R. is supported by an NHMRC Australia Fellowship (AF50); D.I.G. and D.P.F. are supported by NHMRC Senior Principal Research Fellowships (1020770, 1027369).