7T2C

Crystal structure of the B5 TCR in complex with HLA-DP4-Ply

7T2C の概要

• エントリーDOI: 10.2210/pdb7t2c/pdb
• 分子名称: T cell receptor, B5, alpha chain, T cell receptor, B5, beta chain, HLA class II histocompatibility antigen, DP alpha 1 chain, ... (9 entities in total)
• 機能のキーワード: tcr-phla complex, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 95897.70

構造登録者

Ciacchi, L.,Farenc, C.,Petersen, J.,Reid, H.H.,Rossjohn, J. (登録日: 2021-12-03, 公開日: 2022-12-28, 最終更新日: 2024-10-23)

主引用文献

Ciacchi, L.,van de Garde, M.D.B.,Ladell, K.,Farenc, C.,Poelen, M.C.M.,Miners, K.L.,Llerena, C.,Reid, H.H.,Petersen, J.,Price, D.A.,Rossjohn, J.,van Els, C.A.C.M.
CD4 + T cell-mediated recognition of a conserved cholesterol-dependent cytolysin epitope generates broad antibacterial immunity.
Immunity, 56:1082-1097.e6, 2023

PubMed Abstract: CD4 T cell-mediated immunity against Streptococcus pneumoniae (pneumococcus) can protect against recurrent bacterial colonization and invasive pneumococcal diseases (IPDs). Although such immune responses are common, the pertinent antigens have remained elusive. We identified an immunodominant CD4 T cell epitope derived from pneumolysin (Ply), a member of the bacterial cholesterol-dependent cytolysins (CDCs). This epitope was broadly immunogenic as a consequence of presentation by the pervasive human leukocyte antigen (HLA) allotypes DPB102 and DPB104 and recognition via architecturally diverse T cell receptors (TCRs). Moreover, the immunogenicity of Ply was underpinned by core residues in the conserved undecapeptide region (ECTGLAWEWWR), enabling cross-recognition of heterologous bacterial pathogens expressing CDCs. Molecular studies further showed that HLA-DP4-Ply was engaged similarly by private and public TCRs. Collectively, these findings reveal the mechanistic determinants of near-global immune focusing on a trans-phyla bacterial epitope, which could inform ancillary strategies to combat various life-threatening infectious diseases, including IPDs.

PubMed: 37100059
DOI: 10.1016/j.immuni.2023.03.020

実験手法

X-RAY DIFFRACTION (3.1 Å)