MAIT recognition of a stimulatory bacterial antigen bound to MR1

J Immunol. 2013 Nov 15;191(10):5268-77. doi: 10.4049/jimmunol.1301958. Epub 2013 Oct 9.


MR1-restricted mucosal-associated invariant T (MAIT) cells represent a subpopulation of αβ T cells with innate-like properties and limited TCR diversity. MAIT cells are of interest because of their reactivity against bacterial and yeast species, suggesting that they play a role in defense against pathogenic microbes. Despite the advances in understanding MAIT cell biology, the molecular and structural basis behind their ability to detect MR1-Ag complexes is unclear. In this study, we present our structural and biochemical characterization of MAIT TCR engagement of MR1 presenting an Escherichia coli-derived stimulatory ligand, rRL-6-CH2OH, previously found in Salmonella typhimurium. We show a clear enhancement of MAIT TCR binding to MR1 due to the presentation of this ligand. Our structure of a MAIT TCR/MR1/rRL-6-CH2OH complex shows an evolutionarily conserved binding orientation, with a clear role for both the CDR3α and CDR3β loops in recognizing the rRL-6-CH2OH stimulatory ligand. We also present two additional xenoreactive MAIT TCR/MR1 complexes that recapitulate the docking orientation documented previously, despite having variation in the CDR2β and CDR3β loop sequences. Our data support a model by which MAIT TCRs engage MR1 in a conserved fashion, with their binding affinities modulated by the nature of the MR1-presented Ag or diversity introduced by alternate Vβ usage or CDR3β sequences.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigen Presentation / immunology
  • Antigens, Bacterial / immunology*
  • Antigens, Bacterial / ultrastructure
  • Crystallography, X-Ray
  • Escherichia coli / immunology
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Histocompatibility Antigens Class I / ultrastructure
  • Humans
  • Lymphocyte Activation / immunology
  • Minor Histocompatibility Antigens
  • Multiprotein Complexes / ultrastructure*
  • Protein Binding / immunology
  • Protein Structure, Tertiary
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • Receptors, Antigen, T-Cell, alpha-beta / ultrastructure
  • Salmonella typhimurium / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism


  • Antigens, Bacterial
  • Histocompatibility Antigens Class I
  • MR1 protein, human
  • Minor Histocompatibility Antigens
  • Multiprotein Complexes
  • Receptors, Antigen, T-Cell, alpha-beta