Journal article

A class of gamma delta T cell receptors recognize the underside of the antigen-presenting molecule MR1

Jerome Le Nours, Nicholas A Gherardin, Sri H Ramarathinam, Wael Awad, Florian Wiede, Benjamin S Gully, Yogesh Khandokar, T Praveena, Jacinta M Wubben, Jarrod J Sandow, Andrew I Webb, Anouk von Borstel, Michael T Rice, Samuel J Redmond, Rebecca Seneviratna, Maria L Sandoval-Romero, Shihan Li, Michael NT Souter, Sidonia BG Eckle, Alexandra J Corbett Show all

Science | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2019

Abstract

T cell receptors (TCRs) recognize antigens presented by major histocompatibility complex (MHC) and MHC class I-like molecules. We describe a diverse population of human γδ T cells isolated from peripheral blood and tissues that exhibit autoreactivity to the monomorphic MHC-related protein 1 (MR1). The crystal structure of a γδTCR-MR1-antigen complex starkly contrasts with all other TCR-MHC and TCR-MHC-I-like complex structures. Namely, the γδTCR binds underneath the MR1 antigen-binding cleft, where contacts are dominated by the MR1 α3 domain. A similar pattern of reactivity was observed for diverse MR1-restricted γδTCRs from multiple individuals. Accordingly, we simultaneously report MR1 as ..

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Grants

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


Awarded by Australian Research Council (ARC)


Awarded by ARC Future Fellowship


Awarded by NHMRC CDF Fellowship


Awarded by NHMRC Senior Principal Research Fellowships


Awarded by Cancer Council Victoria


Funding Acknowledgements

This work was supported by program grants (1013667, 1016629, and 1113293) and project grants (APP1159932 and APP1100240) from the National Health and Medical Research Council of Australia (NHMRC) and the Australian Research Council (ARC) (CE140100011). N.A.G. was supported by a Leukaemia Foundation of Australia Postgraduate Scholarship and a Cancer Council Victoria postdoctoral fellowship; J.L.N. is supported by an ARC Future Fellowship (FT160100074); A.J.C. is supported by an ARC Future Fellowship (FT160100083); S.B.G.E is supported by an ARC DECRA Fellowship; R.B. is supported by an NHMRC CDF Fellowship (1109901): D.G.P. is supported by an NHMRC CDF Fellowship (1144308); A.P.U. is supported by an ARC Future Fellowship (FT140100278); D.I.G.and D.P.F. are supported by NHMRC Senior Principal Research Fellowships (11177661, 117017); A.W.P. is supported by an NHMRC Principal Research Fellowship: J.R. is supported by an Australian ARC Laureate Fellowship; D.I.G.,J.R, and J.M. are supported by a program grant from the National Health and Medical Research Council of Australia (NHMRC) 1113293; A.P.U. is supported by the Cancer Council Victoria (1126866).