6W9U

Structure of human MAIT A-F7 TCR in complex with patient MR1-R9H-Ac-6-FP

Summary for 6W9U

• Entry DOI: 10.2210/pdb6w9u/pdb
• Descriptor: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, TCR-alpha chain, ... (8 entities in total)
• Functional Keywords: immune system, mait, mr1, metabolite
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 188960.26

Authors

Awad, W.,Rossjohn, J. (deposition date: 2020-03-23, release date: 2020-08-05, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.89 Å)