| Literature DB >> 34083463 |
Stephanie Gras1,2, Jamie Rossjohn1,2,3, Nicole L La Gruta1, Pirooz Zareie4, Christopher Szeto4, Carine Farenc4, Sachith D Gunasinghe5, Elizabeth M Kolawole6, Angela Nguyen4, Chantelle Blyth4, Xavier Y X Sng4, Jasmine Li7, Claerwen M Jones4, Alex J Fulcher8, Jesica R Jacobs6, Qianru Wei9, Lukasz Wojciech9, Jan Petersen4,2, Nicholas R J Gascoigne9, Brian D Evavold6, Katharina Gaus5.
Abstract
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-2Db-NP366 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.Entities:
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Year: 2021 PMID： 34083463 DOI： 10.1126/science.abe9124
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728