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

Jérôme 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 N T Souter; Sidonia B G 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

doi:10.1126/science.aav3900

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

Science. 2019 Dec 20;366(6472):1522-1527. doi: 10.1126/science.aav3900.

Authors

Jérôme Le Nours^{1

2}, Nicholas A Gherardin^{3

4}, Sri H Ramarathinam¹, Wael Awad¹, Florian Wiede^{1

5}, Benjamin S Gully^{1

2}, Yogesh Khandokar¹, T Praveena¹, Jacinta M Wubben¹, Jarrod J Sandow^{6

7}, Andrew I Webb^{6

7}, Anouk von Borstel^{1

2}, Michael T Rice^{1

2}, Samuel J Redmond³, Rebecca Seneviratna³, Maria L Sandoval-Romero¹, Shihan Li^{3

4}, Michael N T Souter³, Sidonia B G Eckle³, Alexandra J Corbett³, Hugh H Reid^{1

2}, Ligong Liu^{8

9}, David P Fairlie^{8

9}, Edward M Giles¹⁰, Glen P Westall^{11

12}, Richard W Tothill^{13

14}, Martin S Davey^{1

2}, Richard Berry^{1

2}, Tony Tiganis^{1

5}, James McCluskey³, Daniel G Pellicci^{3

4}, Anthony W Purcell¹, Adam P Uldrich^{3

4}, Dale I Godfrey^{15

4}, Jamie Rossjohn^{16

2

17}

Affiliations

¹ Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
² Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
³ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.
⁴ Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria 3010, Australia.
⁵ Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
⁶ The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
⁷ Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
⁸ Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
⁹ Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Queensland, Brisbane, Queensland 4072, Australia.
¹⁰ Department of Paediatrics, Monash University, and Centre for Innate Immunity and Infectious Disease, Hudson Institute of Medicine, Clayton, Victoria 3168, Australia.
¹¹ Lung Transplant Service, Alfred Hospital, Melbourne, Victoria 3004, Australia.
¹² Department of Medicine, Monash University, Clayton, Victoria 3800, Australia.
¹³ Department of Clinical Pathology and Centre for Cancer Research, University of Melbourne, Parkville, Victoria 3052, Australia.
¹⁴ The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3000, Australia.
¹⁵ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia. jamie.rossjohn@monash.edu godfrey@unimelb.edu.au.
¹⁶ Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia. jamie.rossjohn@monash.edu godfrey@unimelb.edu.au.
¹⁷ Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.

PMID: 31857486
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 a ligand for human γδ T cells and redefine the parameters for TCR recognition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigen Presentation*
Crystallography, X-Ray
HEK293 Cells
Histocompatibility Antigens Class I / chemistry
Histocompatibility Antigens Class I / immunology*
Humans
Minor Histocompatibility Antigens / chemistry
Minor Histocompatibility Antigens / immunology*
Protein Domains
Receptors, Antigen, T-Cell, gamma-delta / chemistry
Receptors, Antigen, T-Cell, gamma-delta / immunology*

Substances

Histocompatibility Antigens Class I
MR1 protein, human
Minor Histocompatibility Antigens
Receptors, Antigen, T-Cell, gamma-delta