Recognition of vitamin B metabolites by mucosal-associated invariant T cells. Academic Article uri icon

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 alpha-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.

authors

  • Patel, O
  • Kjer-Nielsen, L
  • Le Nours, J
  • Eckle, SBG
  • Birkinshaw, R
  • Beddoe, T
  • Corbett, AJ
  • Liu, L
  • Miles, JJ
  • Meehan, B
  • Reantragoon, R
  • Sandoval-Romero, ML
  • Sullivan, LC
  • Brooks, AG
  • Chen, Z
  • Fairlie, DP
  • McCluskey, J
  • Rossjohn, J

publication date

  • 2013