Canonical T cell receptor docking on peptide-MHC is essential for T cell signaling.
basic_science · Level V
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- Record sourced from PubMed, PMID 34083463.
- Also identified by DOI 10.1126/science.abe9124.
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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<sup>+</sup> TCRs from the naïve mouse CD8<sup>+</sup> T cell repertoire that recognizes the H-2D<sup>b</sup>-NP<sub>366</sub> 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.
Medical subject headings
- CD8-Positive T-Lymphocytes
- Histocompatibility Antigen H-2D
- Nucleocapsid Proteins
- Orthomyxoviridae Infections
- Receptors, Antigen, T-Cell, alpha-beta