Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers.

Autor: Fulford TS; Department of Microbiology & Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia., Soliman C; Department of Microbiology & Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia., Castle RG; Department of Microbiology & Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia., Rigau M; Department of Microbiology & Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.; Institute of Molecular Medicine and Experimental Immunology, Rheinische Friedrichs-Wilhelms University of Bonn, Bonn, Germany.; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Ruan Z; Department of Microbiology & Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia., Dolezal O; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Parkville, Victoria, Australia., Seneviratna R; Department of Microbiology & Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia., Brown HG; Ian Holmes Imaging Centre, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia., Hanssen E; Ian Holmes Imaging Centre, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.; ARC Industrial Transformation Training Centre for Cryo-electron Microscopy of Membrane Proteins, University of Melbourne, Parkville, Victoria, Australia., Hammet A; CSL Limited, Bio21 Molecular Science and Biotechnology Institute, Parkville, Victoria, Australia., Li S; Department of Microbiology & Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia., Redmond SJ; Department of Microbiology & Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia., Chung A; Department of Microbiology & Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia., Gorman MA; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia., Parker MW; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.; ARC Industrial Transformation Training Centre for Cryo-electron Microscopy of Membrane Proteins, University of Melbourne, Parkville, Victoria, Australia.; St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia., Patel O; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia., Peat TS; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Parkville, Victoria, Australia., Newman J; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Parkville, Victoria, Australia., Behren A; Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine, La Trobe University, Heidelberg, Victoria, Australia.; Department of Medicine, University of Melbourne, Parkville, Victoria, Australia., Gherardin NA; Department of Microbiology & Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia., Godfrey DI; Department of Microbiology & Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. godfrey@unimelb.edu.au., Uldrich AP; Department of Microbiology & Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. auldrich@unimelb.edu.au.; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. auldrich@unimelb.edu.au.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Aug; Vol. 25 (8), pp. 1355-1366. Date of Electronic Publication: 2024 Jul 16.
DOI: 10.1038/s41590-024-01892-z
Abstrakt: Butyrophilin (BTN) molecules are emerging as key regulators of T cell immunity; however, how they trigger cell-mediated responses is poorly understood. Here, the crystal structure of a gamma-delta T cell antigen receptor (γδTCR) in complex with BTN2A1 revealed that BTN2A1 engages the side of the γδTCR, leaving the apical TCR surface bioavailable. We reveal that a second γδTCR ligand co-engages γδTCR via binding to this accessible apical surface in a BTN3A1-dependent manner. BTN2A1 and BTN3A1 also directly interact with each other in cis, and structural analysis revealed formation of W-shaped heteromeric multimers. This BTN2A1-BTN3A1 interaction involved the same epitopes that BTN2A1 and BTN3A1 each use to mediate the γδTCR interaction; indeed, locking BTN2A1 and BTN3A1 together abrogated their interaction with γδTCR, supporting a model wherein the two γδTCR ligand-binding sites depend on accessibility to cryptic BTN epitopes. Our findings reveal a new paradigm in immune activation, whereby γδTCRs sense dual epitopes on BTN complexes.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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