4MAY

Crystal structure of an immune complex

4MAY の概要

• エントリーDOI: 10.2210/pdb4may/pdb
• 関連するPDBエントリー: 3PL6 4GRL
• 分子名称: MHC class II HLA-DQ-alpha chain, MHC class II antigen, HY.1B11 TCR alpha chain, ... (6 entities in total)
• 機能のキーワード: immune complex, autoimmunity, multiple sclerosis, antigen presentation, 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: 96746.48

構造登録者

Sethi, D.K.,Wucherpfennig, K.W. (登録日: 2013-08-18, 公開日: 2013-10-23, 最終更新日: 2017-11-15)

主引用文献

Sethi, D.K.,Gordo, S.,Schubert, D.A.,Wucherpfennig, K.W.
Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop.
Nat Commun, 4:2623-2623, 2013

PubMed Abstract: Self-reactive CD4 T cells are thought to have a central role in the pathogenesis of many chronic inflammatory human diseases. Microbial peptides can activate self-reactive T cells, but the structural basis for such crossreactivity is not well understood. The Hy.1B11 T cell receptor (TCR) originates from a patient with multiple sclerosis and recognizes the self-antigen myelin basic protein. Here we report the structural mechanism of TCR crossreactivity with two distinct peptides from human pathogens. The structures show that a single TCR residue (CDR3α F95) makes the majority of contacts with the self-peptide and both microbial peptides (66.7-80.6%) due to a highly tilted TCR-binding topology on the peptide-MHC surface. Further, a neighbouring residue located on the same TCR loop (CDR3α E98) forms an energetically critical interaction with the MHC molecule. These data show how binding by a self-reactive TCR favors crossreactivity between self and microbial antigens.

PubMed: 24136005
DOI: 10.1038/ncomms3623

実験手法

X-RAY DIFFRACTION (2.2 Å)