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

J Le Nours; NA Gherardin; SH Ramarathinam; W Awad; F Wiede; BS Gully; Y Khandokar; T Praveena; JM Wubben; JJ Sandow; AI Webb; A von Borstel; MT Rice; SJ Redmond; R Seneviratna; ML Sandoval-Romero; S Li; MNT Souter; SBG Eckle; AJ Corbett; HH Reid; L Liu; DP Fairlie; EM Giles; GP Westall; RW Tothill; MS Davey; R Berry; T Tiganis; J McCluskey; DG Pellicci; AW Purcell; AP Uldrich; DI Godfrey; J Rossjohn

Journal article

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

J Le Nours, NA Gherardin, SH Ramarathinam, W Awad, F Wiede, BS Gully, Y Khandokar, T Praveena, JM Wubben, JJ Sandow, AI Webb, A von Borstel, MT Rice, SJ Redmond, R Seneviratna, ML Sandoval-Romero, S Li, MNT Souter, SBG Eckle, AJ Corbett Show all

Science | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2019

DOI: 10.1126/science.aav3900

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 gd T cells isolated from peripheral blood and tissues that exhibit autoreactivity to the monomorphic MHC-related protein 1 (MR1). The crystal structure of a gdTCR–MR1–antigen complex starkly contrasts with all other TCR–MHC and TCR–MHC-I-like complex structures. Namely, the gdTCR binds underneath the MR1 antigen-binding cleft, where contacts are dominated by the MR1 a3 domain. A similar pattern of reactivity was observed for diverse MR1-restricted gdTCRs from multiple individuals. Accordingly, we simultaneously report MR1 as ..

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University of Melbourne Researchers

Nicholas Gherardin Author

Andrew Webb Author

Samuel Redmond Author

Shihan Li Author

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Grants

Awarded by National Health and Medical Research Council

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).