7N5C

6218 TCR in complex with H2Db PA with an engineered TCR-pMHC disulfide bond

7N5C の概要

• エントリーDOI: 10.2210/pdb7n5c/pdb
• 分子名称: H-2 class I histocompatibility antigen, D-B alpha chain, Beta-2-microglobulin, peptide from Polymerase acidic protein, ... (7 entities in total)
• 機能のキーワード: major histocompatibility complex, mhc, mouse, influenza a, polymerase acidic protein, h2db, t cell receptor, pa224-233, disulfide bond, cysteine, immune system
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 95324.26

構造登録者

Szeto, C.,Gras, S. (登録日: 2021-06-05, 公開日: 2022-07-20, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.87 Å)