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Review
. 2015 Dec 18;290(51):30204-11.
doi: 10.1074/jbc.R115.685990. Epub 2015 Oct 14.

Recognition of Vitamin B Precursors and Byproducts by Mucosal Associated Invariant T Cells

Sidonia B G Eckle  1 , Alexandra J Corbett  1 , Andrew N Keller  2 , Zhenjun Chen  1 , Dale I Godfrey  3 , Ligong Liu  4 , Jeffrey Y W Mak  4 , David P Fairlie  4 , Jamie Rossjohn  5 , James McCluskey  6
Affiliations
Review

Recognition of Vitamin B Precursors and Byproducts by Mucosal Associated Invariant T Cells

Sidonia B G Eckle et al. J Biol Chem. .

Abstract

Vitamin B2 (riboflavin) is essential for metabolic functions and is synthesized by many bacteria, yeast, and plants, but not by mammals and other animals, which must acquire it from the diet. In mammals, modified pyrimidine intermediates from the microbial biosynthesis of riboflavin are recognized as signature biomarkers of microbial infection. This recognition occurs by specialized lymphocytes known as mucosal associated invariant T (MAIT) cells. The major histocompatibility class I-like antigen-presenting molecule, MR1, captures these pyrimidine intermediates, but only after their condensation with small molecules derived from glycolysis and other metabolic pathways to form short-lived antigens. The resulting MR1-Ag complexes are recognized by MAIT cell antigen receptors (αβ T cell receptors (TCRs)), and the subsequent MAIT cell immune responses are thought to protect the host from pathogens at mucosal surfaces. Here, we review our understanding of how these novel antigens are generated and discuss their interactions with MR1 and MAIT TCRs.

Keywords: Ag presentation; MAIT cells; MR1; T cell recognition; bacterial metabolism; folate; innate immunity; riboflavin; vitamin.

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Figures

FIGURE 1.
FIGURE 1.
Derivation of MR1 ligands from riboflavin synthesis. A, schematic display of the riboflavin biosynthesis pathway. ribH, lumazine synthase; X, hypothetical phosphatase. B, chemical formation of pyrimidines and ribityllumazines from condensation of small metabolites with 5-A-RU. 3,4-DH-2-B-4-P, 3,4-dihydroxy-2-butanone-4-phosphate.
FIGURE 2.
FIGURE 2.
Structural characterization of MR1-binding ligands derived from vitamin B synthetic intermediates. A, ternary structure of MR1 presenting 6-FP to MAIT TCR. Boxed area represents sections shown in more detail in B. B, contact between the MR1 bound antigens 6-FP, RL-6-Me-7-OH, 5-OP-RU, or non-covalently bound 5-OP-RU, with the MAIT TCR. C, contacts sequestering 6-FP, RL-6-Me-7-OH, 5-OP-RU, or non-covalently bound 5-OP-RU within the MR1-binding cleft. D, solvent-accessible area within the MR1-binding cleft with the A′- and F′-pockets labeled. The CDR3α (yellow) and CDR3β (orange) of the MAIT TCR are shown. E, Bistris propane bound within the F′-pocket of MR1 (from PDB ID: 4PJX). All dashed black lines represent hydrogen bonds, and red spheres represent water molecules.
FIGURE 3.
FIGURE 3.
Synthesis of rRL-6-CH2OH and the possible formation of the byproduct 5-OP-RU.
FIGURE 4.
FIGURE 4.
Folic acid and its structurally related MR1 ligands.
See this image and copyright information in PMC

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