6XP6

3C11-DQ2-glia-a2 complex

6XP6 の概要

• エントリーDOI: 10.2210/pdb6xp6/pdb
• 分子名称: MHC class II HLA-DQ-alpha chain, ISOPROPYL ALCOHOL, CHLORIDE ION, ... (12 entities in total)
• 機能のキーワード: complex antibody human leucocyte antigen, peptide binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 192975.41

構造登録者

Petersen, J.,Rossjohn, J. (登録日: 2020-07-08, 公開日: 2021-07-28, 最終更新日: 2024-10-09)

主引用文献

Frick, R.,Hoydahl, L.S.,Petersen, J.,du Pre, M.F.,Kumari, S.,Berntsen, G.,Dewan, A.E.,Jeliazkov, J.R.,Gunnarsen, K.S.,Frigstad, T.,Vik, E.S.,Llerena, C.,Lundin, K.E.A.,Yaqub, S.,Jahnsen, J.,Gray, J.J.,Rossjohn, J.,Sollid, L.M.,Sandlie, I.,Loset, G.A.
A high-affinity human TCR-like antibody detects celiac disease gluten peptide-MHC complexes and inhibits T cell activation.
Sci Immunol, 6:-, 2021

PubMed Abstract: Antibodies specific for peptides bound to human leukocyte antigen (HLA) molecules are valuable tools for studies of antigen presentation and may have therapeutic potential. Here, we generated human T cell receptor (TCR)-like antibodies toward the immunodominant signature gluten epitope DQ2.5-glia-α2 in celiac disease (CeD). Phage display selection combined with secondary targeted engineering was used to obtain highly specific antibodies with picomolar affinity. The crystal structure of a Fab fragment of the lead antibody 3.C11 in complex with HLA-DQ2.5:DQ2.5-glia-α2 revealed a binding geometry and interaction mode highly similar to prototypic TCRs specific for the same complex. Assessment of CeD biopsy material confirmed disease specificity and reinforced the notion that abundant plasma cells present antigen in the inflamed CeD gut. Furthermore, 3.C11 specifically inhibited activation and proliferation of gluten-specific CD4 T cells in vitro and in HLA-DQ2.5 humanized mice, suggesting a potential for targeted intervention without compromising systemic immunity.

PubMed: 34417258
DOI: 10.1126/sciimmunol.abg4925

実験手法

X-RAY DIFFRACTION (2.4 Å)