Canonical T cell receptor docking on peptide-MHC is essential for T cell signaling.
Pirooz Zareie, Christopher Szeto, Carine Farenc, Sachith D Gunasinghe, Elizabeth M Kolawole, Angela Nguyen, Chantelle Blyth, Xavier YX Sng, Jasmine Li, Claerwen M Jones, Alex J Fulcher, Jesica R Jacobs, Qianru Wei, Lukasz Wojciech, Jan Petersen, Nicholas RJ Gascoigne, Brian D Evavold, Katharina Gaus, Stephanie Gras, Jamie Rossjohn Show all
Science | Published : 2021
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. ..View full abstract