2YPL

Structural features underlying T-cell receptor sensitivity to concealed MHC class I micropolymorphisms

2YPL の概要

• エントリーDOI: 10.2210/pdb2ypl/pdb
• 関連するPDBエントリー: 2YPK
• 分子名称: HLA CLASS I HISTOCOMPATIBILITY ANTIGEN, B-57 ALPHA CHAIN, BETA-2-MICROGLOBULIN, KF11 P24 GAG PEPTIDE, ... (6 entities in total)
• 機能のキーワード: immune system-viral protein complex, micropolymorphism, immune system/viral protein
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P18465; Secreted: P61769
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 93725.50

構造登録者

Stewart-Jones, G.B.,Simpson, P.,van der Merwe, P.A.,Easterbrook, P.,McMichael, A.J.,Rowland-Jones, S.L.,Jones, E.Y.,Gillespie, G.M. (登録日: 2012-10-30, 公開日: 2012-11-28, 最終更新日: 2024-11-06)

主引用文献

Stewart-Jones, G.B.,Simpson, P.,Anton Van Der Merwe, P.,Easterbrook, P.,Mcmichael, A.J.,Rowland-Jones, S.L.,Jones, E.Y.,Gillespie, G.M.
Structural Features Underlying T-Cell Receptor Sensitivity to Concealed Mhc Class I Micropolymorphisms.
Proc.Natl.Acad.Sci.USA, 109:E3483-, 2012

PubMed Abstract: Polymorphic differences distinguishing MHC class I subtypes often permit the presentation of shared epitopes in conformationally identical formats but can affect T-cell repertoire selection, differentially impacting autoimmune susceptibilities and viral clearance in vivo. The molecular mechanisms underlying this effect are not well understood. We performed structural, thermodynamic, and functional analyses of a conserved T-cell receptor (TCR) which is frequently expanded in response to a HIV-1 epitope when presented by HLA-B*5701 but is not selected by HLA-B*5703, which differs from HLA-B*5701 by two concealed polymorphisms. Our findings illustrate that although both HLA-B*57 subtypes display the epitope in structurally conserved formats, the impact of their polymorphic differences occurs directly as a consequence of TCR ligation, primarily because of peptide adjustments required for TCR binding, which involves the interplay of polymorphic residues and water molecules. These minor differences culminate in subtype-specific differential TCR-binding kinetics and cellular function. Our data demonstrate a potential mechanism whereby the most subtle MHC class I micropolymorphisms can influence TCR use and highlight their implications for disease outcomes.

PubMed: 23161907
DOI: 10.1073/PNAS.1207896109

実験手法

X-RAY DIFFRACTION (2.4 Å)