4LCW

The structure of human MAIT TCR in complex with MR1-K43A-RL-6-Me-7OH

4LCW の概要

• エントリーDOI: 10.2210/pdb4lcw/pdb
• 関連するPDBエントリー: 4L4V
• 分子名称: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, MAIT T cell receptor alpha chain, ... (7 entities in total)
• 機能のキーワード: mhc class i-related protein, mait t cell receptor, vitamin b2 metabolites, membrane protein-immune system complex, membrane protein/immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Single-pass membrane protein; Extracellular side. Isoform 4: Secreted: Q95460; Secreted: P61769
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 187945.37

構造登録者

Patel, O.,Rossjohn, J. (登録日: 2013-06-24, 公開日: 2013-10-02, 最終更新日: 2024-11-06)

主引用文献

Reantragoon, R.,Corbett, A.J.,Sakala, I.G.,Gherardin, N.A.,Furness, J.B.,Chen, Z.,Eckle, S.B.,Uldrich, A.P.,Birkinshaw, R.W.,Patel, O.,Kostenko, L.,Meehan, B.,Kedzierska, K.,Liu, L.,Fairlie, D.P.,Hansen, T.H.,Godfrey, D.I.,Rossjohn, J.,McCluskey, J.,Kjer-Nielsen, L.
Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells.
J.Exp.Med., 210:2305-2320, 2013

PubMed Abstract: Mucosal-associated invariant T cells (MAIT cells) express a semi-invariant T cell receptor (TCR) α-chain, TRAV1-2-TRAJ33, and are activated by vitamin B metabolites bound by the major histocompatibility complex (MHC)-related class I-like molecule, MR1. Understanding MAIT cell biology has been restrained by the lack of reagents to specifically identify and characterize these cells. Furthermore, the use of surrogate markers may misrepresent the MAIT cell population. We show that modified human MR1 tetramers loaded with the potent MAIT cell ligand, reduced 6-hydroxymethyl-8-D-ribityllumazine (rRL-6-CH₂OH), specifically detect all human MAIT cells. Tetramer(+) MAIT subsets were predominantly CD8(+) or CD4(-)CD8(-), although a small subset of CD4(+) MAIT cells was also detected. Notably, most human CD8(+) MAIT cells were CD8α(+)CD8β(-/lo), implying predominant expression of CD8αα homodimers. Tetramer-sorted MAIT cells displayed a T(H)1 cytokine phenotype upon antigen-specific activation. Similarly, mouse MR1-rRL-6-CH₂OH tetramers detected CD4(+), CD4(-)CD8(-) and CD8(+) MAIT cells in Vα19 transgenic mice. Both human and mouse MAIT cells expressed a broad TCR-β repertoire, and although the majority of human MAIT cells expressed TRAV1-2-TRAJ33, some expressed TRAJ12 or TRAJ20 genes in conjunction with TRAV1-2. Accordingly, MR1 tetramers allow precise phenotypic characterization of human and mouse MAIT cells and revealed unanticipated TCR heterogeneity in this population.

PubMed: 24101382
DOI: 10.1084/jem.20130958

実験手法

X-RAY DIFFRACTION (2.4 Å)