7N5Q

Peptide-MHC complex of mouse H2-Db presenting PA224 with E4C mutation

Summary for 7N5Q

• Entry DOI: 10.2210/pdb7n5q/pdb
• Descriptor: H-2 class I histocompatibility antigen, D-B alpha chain, Beta-2-microglobulin, peptide from Polymerase acidic protein, ... (6 entities in total)
• Functional Keywords: major histocompatibility complex, mhc, mouse, influenza a, polymerase acidic protein, h2db, pa224-233, cysteine, mutant, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 6
• Total formula weight: 91747.93

Authors

Szeto, C.,Gras, S. (deposition date: 2021-06-06, release date: 2022-07-20, Last modification date: 2024-10-23)

Primary citation

Szeto, C.,Zareie, P.,Wirasinha, R.C.,Zhang, J.B.,Nguyen, A.T.,Riboldi-Tunnicliffe, A.,La Gruta, N.L.,Gras, S.,Daley, S.R.
Covalent TCR-peptide-MHC interactions induce T cell activation and redirect T cell fate in the thymus.
Nat Commun, 13:4951-4951, 2022

PubMed Abstract: Interactions between a T cell receptor (TCR) and a peptide-major histocompatibility complex (pMHC) ligand are typically mediated by noncovalent bonds. By studying T cells expressing natural or engineered TCRs, here we describe covalent TCR-pMHC interactions that involve a cysteine-cysteine disulfide bond between the TCR and the peptide. By introducing cysteines into a known TCR-pMHC combination, we demonstrate that disulfide bond formation does not require structural rearrangement of the TCR or the peptide. We further show these disulfide bonds still form even when the initial affinity of the TCR-pMHC interaction is low. Accordingly, TCR-peptide disulfide bonds facilitate T cell activation by pMHC ligands with a wide spectrum of affinities for the TCR. Physiologically, this mechanism induces strong Zap70-dependent TCR signaling, which triggers T cell deletion or agonist selection in the thymus cortex. Covalent TCR-pMHC interactions may thus underlie a physiological T cell activation mechanism that has applications in basic immunology and potentially in immunotherapy.

PubMed: 35999236
DOI: 10.1038/s41467-022-32692-4

Experimental method

X-RAY DIFFRACTION (1.76 Å)