6PY2

HLA-TCR complex

6PY2 の概要

• エントリーDOI: 10.2210/pdb6py2/pdb
• 関連するPDBエントリー: 6PX6
• 分子名称: HLA class II histocompatibility antigen DQ alpha chain, HLA class II histocompatibility antigen DQ beta chain, DQ2.2-glut-L1, ... (8 entities in total)
• 機能のキーワード: hla, mhc, tcr, gluten, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 109952.13

構造登録者

Ting, Y.T.,Peteren, J.,Reid, H.H.,Rossjohn, J. (登録日: 2019-07-28, 公開日: 2020-01-15, 最終更新日: 2024-11-06)

主引用文献

Ting, Y.T.,Dahal-Koirala, S.,Kim, H.S.K.,Qiao, S.W.,Neumann, R.S.,Lundin, K.E.A.,Petersen, J.,Reid, H.H.,Sollid, L.M.,Rossjohn, J.
A molecular basis for the T cell response in HLA-DQ2.2 mediated celiac disease.
Proc.Natl.Acad.Sci.USA, 117:3063-3073, 2020

PubMed Abstract: The highly homologous human leukocyte antigen (HLA)-DQ2 molecules, HLA-DQ2.5 and HLA-DQ2.2, are implicated in the pathogenesis of celiac disease (CeD) by presenting gluten peptides to CD4 T cells. However, while HLA-DQ2.5 is strongly associated with disease, HLA-DQ2.2 is not, and the molecular basis underpinning this differential disease association is unresolved. We here provide structural evidence for how the single polymorphic residue (HLA-DQ2.5-Tyr22α and HLA-DQ2.2-Phe22α) accounts for HLA-DQ2.2 additionally requiring gluten epitopes possessing a serine at the P3 position of the peptide. In marked contrast to the biased T cell receptor (TCR) usage associated with HLA-DQ2.5-mediated CeD, we demonstrate with extensive single-cell sequencing that a diverse TCR repertoire enables recognition of the immunodominant HLA-DQ2.2-glut-L1 epitope. The crystal structure of two CeD patient-derived TCR in complex with HLA-DQ2.2 and DQ2.2-glut-L1 (PFSEQEQPV) revealed a docking strategy, and associated interatomic contacts, which was notably distinct from the structures of the TCR:HLA-DQ2.5:gliadin epitope complexes. Accordingly, while the molecular surfaces of the antigen-binding clefts of HLA-DQ2.5 and HLA-DQ2.2 are very similar, differences in the nature of the peptides presented translates to differences in responding T cell repertoires and the nature of engagement of the respective antigen-presenting molecules, which ultimately is associated with differing disease penetrance.

PubMed: 31974305
DOI: 10.1073/pnas.1914308117

実験手法

X-RAY DIFFRACTION (2.82543430029 Å)