Recognition of vitamin B metabolites by mucosal-associated invariant T cells

Onisha Patel; Lars Kjer-Nielsen; Jérôme Le Nours; Sidonia B G Eckle; Richard Birkinshaw; Travis Beddoe; Alexandra J Corbett; Ligong Liu; John J Miles; Bronwyn Meehan; Rangsima Reantragoon; Maria L Sandoval-Romero; Lucy C Sullivan; Andrew G Brooks; Zhenjun Chen; David P Fairlie; James McCluskey; Jamie Rossjohn

doi:10.1038/ncomms3142

Recognition of vitamin B metabolites by mucosal-associated invariant T cells

Nat Commun. 2013:4:2142. doi: 10.1038/ncomms3142.

Authors

Onisha Patel¹, Lars Kjer-Nielsen, Jérôme Le Nours, Sidonia B G Eckle, Richard Birkinshaw, Travis Beddoe, Alexandra J Corbett, Ligong Liu, John J Miles, Bronwyn Meehan, Rangsima Reantragoon, Maria L Sandoval-Romero, Lucy C Sullivan, Andrew G Brooks, Zhenjun Chen, David P Fairlie, James McCluskey, Jamie Rossjohn

Affiliation

¹ Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.

PMID: 23846752
DOI: 10.1038/ncomms3142

Abstract

The mucosal-associated invariant T-cell antigen receptor (MAIT TCR) recognizes MR1 presenting vitamin B metabolites. Here we describe the structures of a human MAIT TCR in complex with human MR1 presenting a non-stimulatory ligand derived from folic acid and an agonist ligand derived from a riboflavin metabolite. For both vitamin B antigens, the MAIT TCR docks in a conserved manner above MR1, thus acting as an innate-like pattern recognition receptor. The invariant MAIT TCR α-chain usage is attributable to MR1-mediated interactions that prise open the MR1 cleft to allow contact with the vitamin B metabolite. Although the non-stimulatory antigen does not contact the MAIT TCR, the stimulatory antigen does. This results in a higher affinity of the MAIT TCR for a stimulatory antigen in comparison with a non-stimulatory antigen. We formally demonstrate a structural basis for MAIT TCR recognition of vitamin B metabolites, while illuminating how TCRs recognize microbial metabolic signatures.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Crystallography, X-Ray
Escherichia coli / genetics
Folic Acid / chemistry*
Folic Acid / metabolism
Histocompatibility Antigens Class I / chemistry*
Histocompatibility Antigens Class I / immunology
Histocompatibility Antigens Class I / metabolism
Humans
Intestinal Mucosa / cytology
Intestinal Mucosa / immunology
Intestinal Mucosa / metabolism
Jurkat Cells
Minor Histocompatibility Antigens
Molecular Docking Simulation
Protein Interaction Domains and Motifs
Protein Refolding
Receptors, Antigen, T-Cell, alpha-beta / chemistry*
Receptors, Antigen, T-Cell, alpha-beta / immunology
Receptors, Antigen, T-Cell, alpha-beta / metabolism
Recombinant Proteins / chemistry
Recombinant Proteins / immunology
Recombinant Proteins / metabolism
Riboflavin / chemistry*
Riboflavin / metabolism
T-Lymphocytes / cytology
T-Lymphocytes / immunology
T-Lymphocytes / metabolism*

Substances

Histocompatibility Antigens Class I
MR1 protein, human
Minor Histocompatibility Antigens
Receptors, Antigen, T-Cell, alpha-beta
Recombinant Proteins
Folic Acid
Riboflavin

Associated data

PDB/4L4T
PDB/4L4V