5LAX

Crystal structure of HLA_DRB1*04:01 in complex with alpha-enolase peptide 26-40

5LAX の概要

• エントリーDOI: 10.2210/pdb5lax/pdb
• 分子名称: HLA class II histocompatibility antigen, DR alpha chain, HLA class II histocompatibility antigen, DRB1-4 beta chain, alpha-enolase peptideTSKGLFRAAVPSGAS, ... (5 entities in total)
• 機能のキーワード: hla, autoimmune desease, rheumathoid arthritis, mhc class ii, 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 P13760
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 93034.18

構造登録者

Dubnovitsky, A.,Kozhukh, G.,Sandalova, T.,Achour, A. (登録日: 2016-06-15, 公開日: 2016-12-07, 最終更新日: 2024-11-20)

主引用文献

Gerstner, C.,Dubnovitsky, A.,Sandin, C.,Kozhukh, G.,Uchtenhagen, H.,James, E.A.,Ronnelid, J.,Ytterberg, A.J.,Pieper, J.,Reed, E.,Tandre, C.,Rieck, M.,Zubarev, R.A.,Ronnblom, L.,Sandalova, T.,Buckner, J.H.,Achour, A.,Malmstrom, V.
Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted alpha-Enolase T Cell Epitope in Rheumatoid Arthritis.
Front Immunol, 7:494-494, 2016

PubMed Abstract: Antibodies to citrullinated proteins, common in rheumatoid arthritis (RA) patients, are strongly associated to a specific set of HLA-DR alleles including HLA-DRB1*04:01, *04:04, and *01:01. Here, we first demonstrate that autoantibody levels toward the dominant citrullinated B cell epitope from α-enolase are significantly elevated in HLA-DRB1*04:01-positive RA patients. Furthermore, we identified α-enolase-derived T cell epitopes and demonstrated that native and citrullinated versions of several peptides bind with different affinities to HLA-DRB1*04:01, *04:04, and *01:01. The citrulline residues in the eight identified peptides are distributed throughout the entire length of the presented epitopes and more specifically, localized at peptide positions p-2, p2, p4, p6, p7, p10, and p11. Importantly, in contrast to its native version peptide 26 (TSKGLFAAVPSGAS), the HLA-DRB1*04:01-restricted citrullinated peptide Cit26 (TSKGLFAAVPSGAS) elicited significant functional T cell responses in primary cells from RA patients. Comparative analysis of the crystal structures of HLA-DRB1*04:01 in complex with peptide 26 or Cit26 demonstrated that the posttranslational modification did not alter the conformation of the peptide. And since citrullination is the only structural difference between the two complexes, this indicates that the neo-antigen Cit26 is recognized by T cells with high specificity to the citrulline residue.

PubMed: 27895642
DOI: 10.3389/fimmu.2016.00494

実験手法

X-RAY DIFFRACTION (2.6 Å)