5MEP

Human Leukocyte Antigen A02 presenting ILGKFLHWL

5MEP の概要

• エントリーDOI: 10.2210/pdb5mep/pdb
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, ILE-LEU-GLY-LYS-PHE-LEU-HIS-TRP-LEU, ... (6 entities in total)
• 機能のキーワード: hla a02, hlaa, mhc, immuno, telomerase, immune system
• 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: P01892; Secreted . Note=(Microbial infection) In the presence of M: P61769
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 90696.97

構造登録者

Rizkallah, P.J.,Cole, D.K.,Lloyd, A.,Crowther, M.,Sewell, A.K. (登録日: 2016-11-16, 公開日: 2016-12-07, 最終更新日: 2024-10-16)

主引用文献

Cole, D.K.,van den Berg, H.A.,Lloyd, A.,Crowther, M.D.,Beck, K.,Ekeruche-Makinde, J.,Miles, J.J.,Bulek, A.M.,Dolton, G.,Schauenburg, A.J.,Wall, A.,Fuller, A.,Clement, M.,Laugel, B.,Rizkallah, P.J.,Wooldridge, L.,Sewell, A.K.
Structural Mechanism Underpinning Cross-reactivity of a CD8+ T-cell Clone That Recognizes a Peptide Derived from Human Telomerase Reverse Transcriptase.
J. Biol. Chem., 292:802-813, 2017

PubMed Abstract: T-cell cross-reactivity is essential for effective immune surveillance but has also been implicated as a pathway to autoimmunity. Previous studies have demonstrated that T-cell receptors (TCRs) that focus on a minimal motif within the peptide are able to facilitate a high level of T-cell cross-reactivity. However, the structural database shows that most TCRs exhibit less focused antigen binding involving contact with more peptide residues. To further explore the structural features that allow the clonally expressed TCR to functionally engage with multiple peptide-major histocompatibility complexes (pMHCs), we examined the ILA1 CD8 T-cell clone that responds to a peptide sequence derived from human telomerase reverse transcriptase. The ILA1 TCR contacted its pMHC with a broad peptide binding footprint encompassing spatially distant peptide residues. Despite the lack of focused TCR-peptide binding, the ILA1 T-cell clone was still cross-reactive. Overall, the TCR-peptide contacts apparent in the structure correlated well with the level of degeneracy at different peptide positions. Thus, the ILA1 TCR was less tolerant of changes at peptide residues that were at, or adjacent to, key contact sites. This study provides new insights into the molecular mechanisms that control T-cell cross-reactivity with important implications for pathogen surveillance, autoimmunity, and transplant rejection.

PubMed: 27903649
DOI: 10.1074/jbc.M116.741603

実験手法

X-RAY DIFFRACTION (2.71 Å)