4Z7W

T316 complex

4Z7W の概要

• エントリーDOI: 10.2210/pdb4z7w/pdb
• 関連するPDBエントリー: 4Z7U 4Z7V
• 分子名称: MHC class II HLA-DQ-alpha chain, MHC class II HLA-DQ-beta-1, T-CELL RECEPTOR, T316 ALPHA CHAIN, ... (9 entities in total)
• 機能のキーワード: immune receptor-ligand 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: 10
• 化学式量合計: 199550.36

構造登録者

Petersen, J.,Rossjohn, J.,Reid, H.H.,Koning, F. (登録日: 2015-04-08, 公開日: 2015-06-03, 最終更新日: 2024-10-16)

主引用文献

Petersen, J.,van Bergen, J.,Loh, K.L.,Kooy-Winkelaar, Y.,Beringer, D.X.,Thompson, A.,Bakker, S.F.,Mulder, C.J.,Ladell, K.,McLaren, J.E.,Price, D.A.,Rossjohn, J.,Reid, H.H.,Koning, F.
Determinants of Gliadin-Specific T Cell Selection in Celiac Disease.
J Immunol., 194:6112-6122, 2015

PubMed Abstract: In HLA-DQ8-associated celiac disease (CD), the pathogenic T cell response is directed toward an immunodominant α-gliadin-derived peptide (DQ8-glia-α1). However, our knowledge of TCR gene usage within the primary intestinal tissue of HLA-DQ8 (+) CD patients is limited. We identified two populations of HLA-DQ8-glia-α1 tetramer(+) CD4(+) T cells that were essentially undetectable in biopsy samples from patients on a gluten-free diet but expanded rapidly and specifically after antigenic stimulation. Distinguished by expression of TRBV9, both T cell populations displayed biased clonotypic repertoires and reacted similarly against HLA-DQ8-glia-α1. In particular, TRBV9 paired most often with TRAV26-2, whereas the majority of TRBV9(-) TCRs used TRBV6-1 with no clear TRAV gene preference. Strikingly, both tetramer(+)/TRBV9(+) and tetramer(+)/TRBV9(-) T cells possessed a non-germline-encoded arginine residue in their CDR3α and CDR3β loops, respectively. Comparison of the crystal structures of three TRBV9(+) TCRs and a TRBV9(-) TCR revealed that, as a result of distinct TCR docking modes, the HLA-DQ8-glia-α1 contacts mediated by the CDR3-encoded arginine were almost identical between TRBV9(+) and TRBV9(-) TCRs. In all cases, this interaction centered on two hydrogen bonds with a specific serine residue in the bound peptide. Replacement of serine with alanine at this position abrogated TRBV9(+) and TRBV9(-) clonal T cell proliferation in response to HLA-DQ8-glia-α1. Gluten-specific memory CD4(+) T cells with structurally and functionally conserved TCRs therefore predominate in the disease-affected tissue of patients with HLA-DQ8-mediated CD.

PubMed: 25948817
DOI: 10.4049/jimmunol.1500161

実験手法

X-RAY DIFFRACTION (2.89 Å)