Canonical T cell receptor docking on peptide-MHC is essential for T cell signaling.

Autor: Zareie P; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Szeto C; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Farenc C; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Gunasinghe SD; European Molecular Biology Laboratory (EMBL) Australia Node in Single Molecule Science and the ARC Centre of Excellence in Advanced Molecular Imaging, School of Medical Sciences, University of New South Wales, New South Wales, Australia., Kolawole EM; Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA., Nguyen A; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Blyth C; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Sng XYX; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Li J; Infection and Immunity Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Jones CM; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Fulcher AJ; Monash Micro Imaging, Monash University, Clayton, Victoria, Australia., Jacobs JR; Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA., Wei Q; Immunology Translational Research Programme and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545., Wojciech L; Immunology Translational Research Programme and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545., Petersen J; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia., Gascoigne NRJ; Immunology Translational Research Programme and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545., Evavold BD; Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA., Gaus K; European Molecular Biology Laboratory (EMBL) Australia Node in Single Molecule Science and the ARC Centre of Excellence in Advanced Molecular Imaging, School of Medical Sciences, University of New South Wales, New South Wales, Australia., Gras S; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. nicole.la.gruta@monash.edu jamie.rossjohn@monash.edu s.gras@latrobe.edu.au.; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia., Rossjohn J; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. nicole.la.gruta@monash.edu jamie.rossjohn@monash.edu s.gras@latrobe.edu.au.; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.; Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK., La Gruta NL; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. nicole.la.gruta@monash.edu jamie.rossjohn@monash.edu s.gras@latrobe.edu.au.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2021 Jun 04; Vol. 372 (6546).
DOI: 10.1126/science.abe9124
Abstrakt: T cell receptor (TCR) recognition of peptide-major histocompatibility complexes (pMHCs) is characterized by a highly conserved docking polarity. Whether this polarity is driven by recognition or signaling constraints remains unclear. Using "reversed-docking" TCRβ-variable (TRBV) 17 + TCRs from the naïve mouse CD8 + T cell repertoire that recognizes the H-2D b -NP 366 epitope, we demonstrate that their inability to support T cell activation and in vivo recruitment is a direct consequence of reversed docking polarity and not TCR-pMHCI binding or clustering characteristics. Canonical TCR-pMHCI docking optimally localizes CD8/Lck to the CD3 complex, which is prevented by reversed TCR-pMHCI polarity. The requirement for canonical docking was circumvented by dissociating Lck from CD8. Thus, the consensus TCR-pMHC docking topology is mandated by T cell signaling constraints.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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