8VZ8

Crystal structure of mouse MAIT M2B TCR-MR1-5-OP-RU complex

8VZ8 の概要

• エントリーDOI: 10.2210/pdb8vz8/pdb
• 分子名称: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, Mouse MAIT TRAV1-TRAJ33 a-chain, ... (6 entities in total)
• 機能のキーワード: mouse mait tcr recognition of mr1, immune system
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 93668.36

構造登録者

Ciacchi, L.,Rossjohn, J.,Awad, W. (登録日: 2024-02-11, 公開日: 2024-04-10, 最終更新日: 2024-11-06)

主引用文献

Ciacchi, L.,Mak, J.Y.W.,Le, J.P.,Fairlie, D.P.,McCluskey, J.,Corbett, A.J.,Rossjohn, J.,Awad, W.
Mouse mucosal-associated invariant T cell receptor recognition of MR1 presenting the vitamin B metabolite, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil.
J.Biol.Chem., 300:107229-107229, 2024

PubMed Abstract: Mucosal-associated invariant T (MAIT) cells can elicit immune responses against riboflavin-based antigens presented by the evolutionary conserved MHC class I related protein, MR1. While we have an understanding of the structural basis of human MAIT cell receptor (TCR) recognition of human MR1 presenting a variety of ligands, how the semi-invariant mouse MAIT TCR binds mouse MR1-ligand remains unknown. Here, we determine the crystal structures of 2 mouse TRAV1-TRBV13-2 MAIT TCR-MR1-5-OP-RU ternary complexes, whose TCRs differ only in the composition of their CDR3β loops. These mouse MAIT TCRs mediate high affinity interactions with mouse MR1-5-OP-RU and cross-recognize human MR1-5-OP-RU. Similarly, a human MAIT TCR could bind mouse MR1-5-OP-RU with high affinity. This cross-species recognition indicates the evolutionary conserved nature of this MAIT TCR-MR1 axis. Comparing crystal structures of the mouse versus human MAIT TCR-MR1-5-OP-RU complexes provides structural insight into the conserved nature of this MAIT TCR-MR1 interaction and conserved specificity for the microbial antigens, whereby key germline-encoded interactions required for MAIT activation are maintained. This is an important consideration for the development of MAIT cell-based therapeutics that will rely on preclinical mouse models of disease.

PubMed: 38537698
DOI: 10.1016/j.jbc.2024.107229

実験手法

X-RAY DIFFRACTION (3.45 Å)