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; Hugh H Reid; Ligong Liu; David P Fairlie; Edward M Giles; Glen P Westall; Richard W Tothill; Martin S Davey; Richard Berry; Tony Tiganis; James McCluskey; Daniel G Pellicci; Anthony W Purcell; Adam P Uldrich; Dale I Godfrey; Jamie Rossjohn

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

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 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 ..

View full abstract

University of Melbourne Researchers

Dale Godfrey Author Microbiology and Immunology

Alexandra Corbett Author Microbiology and Immunology

Shihan Li Author Microbiology and Immunology

Nicholas Gherardin Author Microbiology and Immunology

Related Projects (7)

IMMUNE REGULATION EFFECTOR FUNCTION AND THERAPY

We seek to understand how white blood cells detect and destroy disease, and how molecules of the immune system punch holes in diseased cells..

ANTIGEN PRESENTATION RECOGNITION AND THE IMMUNE SYSTEM

This program focuses on understanding the development of immune response to viruses and other infectious agents using a broad array of techn..

RECOGNITION OF LIPID ANTIGENS BY THE IMMUNE SYSTEM.

T cells are a critical component of the immune system, protecting against a range of pathogens by detecting and responding to foreign molecu..

ANTIGEN PRESENTATION, RECOGNITION AND THE IMMUNE RESPONSE

This program focuses on understanding the development of immunity during infection or inflammatory diseases using a broad array of technique..

UNCONVENTIONAL T CELLS IN HEALTH AND DISEASE

The human immune system comprises many different types of cells that can detect foreign molecules. My research will lead the way to understa..

THE ROLE OF CD1-RESTRICTED T CELLS IN HEALTH AND DISEASE

The human immune system requires T cells for survival. Specialised populations of T cells exist that patrol the body and target unwanted lip..

Understanding recognition of vitamin B-based antigens by the immune system

This project aims to evaluate the range of molecules that can stimulate vitamin B-reactive T cells in mammals and amphibians, and the degree..

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

Awarded by National Health and Medical Research Council of Australia

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).