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

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 naive mouse CD8(+) T cell repertoire that recognizes the H-2D(b)-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.

Automated summary

The study found that the T cell receptor recognizes peptide-major histocompatibility complexes with a highly conserved docking polarity, which affects T cell activation and recruitment in vivo. The canonical docking of TCR-pMHCI is essential for optimal T cell signaling.