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

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

Author information

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.

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.

PMID:
31857486
DOI:
10.1126/science.aav3900

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