3UTP

1E6 TCR specific for HLA-A*0201-ALWGPDPAAA

3UTP の概要

• エントリーDOI: 10.2210/pdb3utp/pdb
• 関連するPDBエントリー: 3UTQ 3UTS 3UTT
• 分子名称: 1E6 TCR alpha chain, 1E6 TCR beta chain, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: t cell receptor, type i diabetes, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 102536.99

構造登録者

Rizkallah, P.J.,Cole, D.K.,Sewell, A.K.,Bulek, A.M. (登録日: 2011-11-26, 公開日: 2012-01-25, 最終更新日: 2024-11-27)

主引用文献

Bulek, A.M.,Cole, D.K.,Skowera, A.,Dolton, G.,Gras, S.,Madura, F.,Fuller, A.,Miles, J.J.,Gostick, E.,Price, D.A.,Drijfhout, J.W.,Knight, R.R.,Huang, G.C.,Lissin, N.,Molloy, P.E.,Wooldridge, L.,Jakobsen, B.K.,Rossjohn, J.,Peakman, M.,Rizkallah, P.J.,Sewell, A.K.
Structural basis for the killing of human beta cells by CD8(+) T cells in type 1 diabetes.
Nat.Immunol., 13:283-289, 2012

PubMed Abstract: The structural characteristics of the engagement of major histocompatibility complex (MHC) class II-restricted self antigens by autoreactive T cell antigen receptors (TCRs) is established, but how autoimmune TCRs interact with complexes of self peptide and MHC class I has been unclear. Here we examined how CD8(+) T cells kill human islet beta cells in type 1 diabetes via recognition of a human leukocyte antigen HLA-A*0201-restricted glucose-sensitive preproinsulin peptide by the autoreactive TCR 1E6. Rigid 'lock-and-key' binding underpinned the 1E6-HLA-A*0201-peptide interaction, whereby 1E6 docked similarly to most MHC class I-restricted TCRs. However, this interaction was extraordinarily weak because of limited contacts with MHC class I. TCR binding was highly peptide centric, dominated by two residues of the complementarity-determining region 3 (CDR3) loops that acted as an 'aromatic-cap' over the complex of peptide and MHC class I (pMHCI). Thus, highly focused peptide-centric interactions associated with suboptimal TCR-pMHCI binding affinities might lead to thymic escape and potential CD8(+) T cell-mediated autoreactivity.

PubMed: 22245737
DOI: 10.1038/ni.2206

実験手法

X-RAY DIFFRACTION (2.574 Å)