Journal article
Canonical T cell receptor docking on peptide–MHC is essential for T cell signaling
P Zareie, C Szeto, C Farenc, SD Gunasinghe, EM Kolawole, A Nguyen, C Blyth, XYX Sng, J Li, CM Jones, AJ Fulcher, JR Jacobs, Q Wei, L Wojciech, J Petersen, NRJ Gascoigne, BD Evavold, K Gaus, S Gras, J Rossjohn Show all
Science | Published : 2021
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” TCRb-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 abstractGrants
Awarded by Australian Research Council (ARC)
Awarded by National Health and Medical Research Council of Australia (NHMRC)
Awarded by NSW Cancer Council
Awarded by Singapore Ministry of Health's National Medical Research Council
Awarded by Singapore Ministry of Education
Funding Acknowledgements
This work was supported by the Australian Research Council (ARC) (DP170103631 to N.L.L. and S.G., DP201102776 to N. L.L., CE140100011 to J.R. and K.G.); the National Health and Medical Research Council of Australia (NHMRC) (APP1182086 to N.L.L. and APP1155162 to K.G.); the NSW Cancer Council (APP1128488 to K.G.); the Singapore Ministry of Health's National Medical Research Council (CBRG/0097/2015 to N.R.J.G.); and the Singapore Ministry of Education (2014-T2-1136 to N.R.J.G.). N.L. L. is supported by an ARC Future Fellowship, S.G. by an NHMRC Senior Research Fellowship, and J.R. by an ARC Laureate Fellowship.