2IAM

Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR

2IAM の概要

• エントリーDOI: 10.2210/pdb2iam/pdb
• 関連するPDBエントリー: 1KLG 1KLU 2IAL 2IAN
• 分子名称: HLA class II histocompatibility antigen, DR alpha chain, HLA class II histocompatibility antigen, DRB1-1 beta chain, 15-mer peptide from Triosephosphate isomerase, ... (6 entities in total)
• 機能のキーワード: major histocompatibility complex, t cell receptor, t cell stimulation, melanoma, tumor antigen, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: P01903 P04229; Membrane; Single-pass membrane protein (Potential): P01848 P01850
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 94206.16

構造登録者

Deng, L.,Langley, R.J.,Mariuzza, R.A. (登録日: 2006-09-08, 公開日: 2007-04-03, 最終更新日: 2023-10-25)

主引用文献

Deng, L.,Langley, R.J.,Brown, P.H.,Xu, G.,Teng, L.,Wang, Q.,Gonzales, M.I.,Callender, G.G.,Nishimura, M.I.,Topalian, S.L.,Mariuzza, R.A.
Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor
Nat.Immunol., 8:398-408, 2007

PubMed Abstract: Structural studies of complexes of T cell receptor (TCR) and peptide-major histocompatibility complex (MHC) have focused on TCRs specific for foreign antigens or native self. An unexplored category of TCRs includes those specific for self determinants bearing alterations resulting from disease, notably cancer. We determined here the structure of a human melanoma-specific TCR (E8) bound to the MHC molecule HLA-DR1 and an epitope from mutant triosephosphate isomerase. The structure had features intermediate between 'anti-foreign' and autoimmune TCR-peptide-MHC class II complexes that may reflect the hybrid nature of altered self. E8 manifested very low affinity for mutant triosephosphate isomerase-HLA-DR1 despite the highly tumor-reactive properties of E8 cells. A second TCR (G4) had even lower affinity but underwent peptide-specific formation of dimers, suggesting this as a mechanism for enhancing low-affinity TCR-peptide-MHC interactions for T cell activation.

PubMed: 17334368
DOI: 10.1038/ni1447

実験手法

X-RAY DIFFRACTION (2.8 Å)