6W9V

Structure of human MAIT A-F7 TCR in complex with patient MR1-R9H without ligand

6W9V の概要

• エントリーDOI: 10.2210/pdb6w9v/pdb
• 分子名称: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, TCR-alpha chain, ... (7 entities in total)
• 機能のキーワード: immune system, mait, mr1, metabolite
• 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: 188548.48

構造登録者

Awad, W.,Rossjohn, J. (登録日: 2020-03-23, 公開日: 2020-08-05, 最終更新日: 2024-11-06)

主引用文献

Howson, L.J.,Awad, W.,von Borstel, A.,Lim, H.J.,McWilliam, H.E.G.,Sandoval-Romero, M.L.,Majumdar, S.,Hamzeh, A.R.,Andrews, T.D.,McDermott, D.H.,Murphy, P.M.,Le Nours, J.,Mak, J.Y.W.,Liu, L.,Fairlie, D.P.,McCluskey, J.,Villadangos, J.A.,Cook, M.C.,Turner, S.J.,Davey, M.S.,Ojaimi, S.,Rossjohn, J.
Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1 .
Sci Immunol, 5:-, 2020

PubMed Abstract: The role unconventional T cells play in protective immunity in humans is unclear. Mucosal-associated invariant T (MAIT) cells are an unconventional T cell subset restricted to the antigen-presenting molecule MR1. Here, we report the discovery of a patient homozygous for a rare Arg31His (R9H in the mature protein) mutation in MR1 who has a history of difficult-to-treat viral and bacterial infections. MR1 was unable to present the potent microbially derived MAIT cell stimulatory ligand. The MR1 crystal structure revealed that the stimulatory ligand cannot bind due to the mutation lying within, and causing structural perturbation to, the ligand-binding domain of MR1. While MR1 could bind and be up-regulated by a MAIT cell inhibitory ligand, the patient lacked circulating MAIT cells. This shows the importance of the stimulatory ligand for MAIT cell selection in humans. The patient had an expanded γδ T cell population, indicating a compensatory interplay between these unconventional T cell subsets.

PubMed: 32709702
DOI: 10.1126/sciimmunol.abc9492

実験手法

X-RAY DIFFRACTION (1.95 Å)