9BTY

Structure of human MAIT A-F7 TCR in complex with human MR1-veratraldehyde

9BTY の概要

• エントリーDOI: 10.2210/pdb9bty/pdb
• 分子名称: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, Human TCR TRAV1-2_ALPHA, ... (8 entities in total)
• 機能のキーワード: antigen presentation, mait cells, t cell receptor, mr1, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 188951.97

構造登録者

Awad, W.,Rossjohn, J. (登録日: 2024-05-15, 公開日: 2024-12-25, 最終更新日: 2025-01-29)

主引用文献

Awad, W.,Mayall, J.R.,Xu, W.,Johansen, M.D.,Patton, T.,Lim, X.Y.,Galvao, I.,Howson, L.J.,Brown, A.C.,Haw, T.J.,Donovan, C.,Das, S.,Albers, G.J.,Pai, T.Y.,Hortle, E.,Gillis, C.M.,Hansbro, N.G.,Horvat, J.C.,Liu, L.,Mak, J.Y.W.,McCluskey, J.,Fairlie, D.P.,Corbett, A.J.,Hansbro, P.M.,Rossjohn, J.
Cigarette smoke components modulate the MR1-MAIT axis.
J.Exp.Med., 222:-, 2025

PubMed Abstract: Tobacco smoking is prevalent across the world and causes numerous diseases. Cigarette smoke (CS) compromises immunity, yet little is known of the components of CS that impact T cell function. MR1 is a ubiquitous molecule that presents bacterial metabolites to MAIT cells, which are highly abundant in the lungs. Using in silico, cellular, and biochemical approaches, we identified components of CS that bind MR1 and impact MR1 cell surface expression. Compounds, including nicotinaldehyde, phenylpropanoid, and benzaldehyde-related scaffolds, bound within the A' pocket of MR1. CS inhibited MAIT cell activation, ex vivo, via TCR-dependent and TCR-independent mechanisms. Chronic CS exposure altered MAIT cell phenotype and function and attenuated MAIT cell responses to influenza A virus infection in vivo. MR1-deficient mice were partially protected from the development of chronic obstructive pulmonary disease (COPD) features that were associated with CS exposure. Thus, CS can impair MAIT cell function by diverse mechanisms, and potentially contribute to infection susceptibility and disease exacerbations.

PubMed: 39820322
DOI: 10.1084/jem.20240896

実験手法

X-RAY DIFFRACTION (2.85 Å)