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Publication Abstract from PubMed

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" TCRbeta-variable (TRBV) 17(+) TCRs from the naive 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.

Canonical T cell receptor docking on peptide-MHC is essential for T cell signaling.,Zareie P, Szeto C, Farenc C, Gunasinghe SD, Kolawole EM, Nguyen A, Blyth C, Sng XYX, Li J, Jones CM, Fulcher AJ, Jacobs JR, Wei Q, Wojciech L, Petersen J, Gascoigne NRJ, Evavold BD, Gaus K, Gras S, Rossjohn J, La Gruta NL Science. 2021 Jun 4;372(6546):eabe9124. doi: 10.1126/science.abe9124. PMID:34083463^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.