An overview on the identification of MAIT cell antigens

Lars Kjer-Nielsen, Alexandra J. Corbett, Zhenjun Chen, Ligong Liu, Jeffrey Yw Mak, Dale I. Godfrey, Jamie Rossjohn, David P. Fairlie, James Mccluskey, Sidonia Bg Eckle

Research output: Contribution to journalArticleResearchpeer-review

32 Citations (Scopus)

Abstract

Mucosal associated invariant T (MAIT) cells are restricted by the monomorphic MHC class I-like molecule, MHC-related protein-1 (MR1). Until 2012, the origin of the MAIT cell antigens (Ags) was unknown, although it was established that MAIT cells could be activated by a broad range of bacteria and yeasts, possibly suggesting a conserved Ag. Using a combination of protein chemistry, mass spectrometry, cellular biology, structural biology and small molecule chemistry, we discovered MR1 ligands derived from folic acid (vitamin B9) and from an intermediate in the microbial biosynthesis of riboflavin (vitamin B2). While the folate derivative 6-formylpterin generally inhibited MAIT cell activation, two riboflavin pathway derivatives, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil, were potent MAIT cell agonists. Other intermediates and derivatives of riboflavin synthesis displayed weak or no MAIT cell activation. Collectively, these studies revealed that in addition to peptide and lipid-based Ags, small molecule natural product metabolites are also ligands that can activate T cells expressing αβ T-cell receptors, and here we recount this discovery.

Original languageEnglish
Pages (from-to)573-587
Number of pages15
JournalImmunology and Cell Biology
Volume96
Issue number6
DOIs
Publication statusPublished - Jul 2018

Keywords

  • 5-(2-oxoethylideneamino)-6-d-ribityl-aminouracil
  • 5-(2-oxopropylidene-amino)-6-d-ribitylaminouracil
  • 5-A-RU
  • 5-amino-6-d-ribitylaminouracil
  • 5-OE-RU
  • 5-OP-RU
  • Antigen
  • Folic acid
  • MAIT cells
  • MR1
  • Mucosal associated invariant T cells
  • Riboflavin
  • T-cell receptor
  • TCR
  • Vitamin B

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