6XC9

Immune receptor complex

6XC9 の概要

• エントリーDOI: 10.2210/pdb6xc9/pdb
• 分子名称: MHC class II HLA-DQ-alpha chain, Hybrid Insulin Peptide, MHC class II HLA-DQ-beta chain fusion, T-CELL-RECEPTOR, A3.10-alpha chain, ... (9 entities in total)
• 機能のキーワード: immune complex, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 200505.82

構造登録者

Tran, T.M.,Faridi, P.,Lim, J.J.,Ting, T.Y.,Onwukwe, G.,Bhattacharjee, P.,Tresoldi, M.C.E.,Cameron, J.F.,La-Gruta, L.N.,Purcell, W.A.,Mannering, I.S.,Rossjohn, J.,Reid, H.H. (登録日: 2020-06-08, 公開日: 2021-07-14, 最終更新日: 2024-10-30)

主引用文献

Tran, M.T.,Faridi, P.,Lim, J.J.,Ting, Y.T.,Onwukwe, G.,Bhattacharjee, P.,Jones, C.M.,Tresoldi, E.,Cameron, F.J.,La Gruta, N.L.,Purcell, A.W.,Mannering, S.I.,Rossjohn, J.,Reid, H.H.
T cell receptor recognition of hybrid insulin peptides bound to HLA-DQ8.
Nat Commun, 12:5110-5110, 2021

PubMed Abstract: HLA-DQ8, a genetic risk factor in type I diabetes (T1D), presents hybrid insulin peptides (HIPs) to autoreactive CD4+ T cells. The abundance of spliced peptides binding to HLA-DQ8 and how they are subsequently recognised by the autoreactive T cell repertoire is unknown. Here we report, the HIP (GQVELGGGNAVEVLK), derived from splicing of insulin and islet amyloid polypeptides, generates a preferred peptide-binding motif for HLA-DQ8. HLA-DQ8-HIP tetramer T cells from the peripheral blood of a T1D patient are characterised by repeated TRBV5 usage, which matches the TCR bias of CD4+ T cells reactive to the HIP peptide isolated from the pancreatic islets of a patient with T1D. The crystal structure of three TRBV5+ TCR-HLA-DQ8-HIP complexes shows that the TRBV5-encoded TCR β-chain forms a common landing pad on the HLA-DQ8 molecule. The N- and C-termini of the HIP is recognised predominantly by the TCR α-chain and TCR β-chain, respectively, in all three TCR ternary complexes. Accordingly, TRBV5 + TCR recognition of HIP peptides might occur via a 'polarised' mechanism, whereby each chain within the αβTCR heterodimer recognises distinct origins of the spliced peptide presented by HLA-DQ8.

PubMed: 34433824
DOI: 10.1038/s41467-021-25404-x

実験手法

X-RAY DIFFRACTION (2.4 Å)