The intracellular pathway for the presentation of vitamin B-related antigens by the antigen-presenting molecule MR1

Nat Immunol. 2016 May;17(5):531-7. doi: 10.1038/ni.3416. Epub 2016 Apr 4.


The antigen-presenting molecule MR1 presents vitamin B-related antigens (VitB antigens) to mucosal-associated invariant T (MAIT) cells through an uncharacterized pathway. We show that MR1, unlike other antigen-presenting molecules, does not constitutively present self-ligands. In the steady state it accumulates in a ligand-receptive conformation within the endoplasmic reticulum. VitB antigens reach this location and form a Schiff base with MR1, triggering a 'molecular switch' that allows MR1-VitB antigen complexes to traffic to the plasma membrane. These complexes are endocytosed with kinetics independent of the affinity of the MR1-ligand interaction and are degraded intracellularly, although some MR1 molecules acquire new ligands during passage through endosomes and recycle back to the surface. MR1 antigen presentation is characterized by a rapid 'off-on-off' mechanism that is strictly dependent on antigen availability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology*
  • Antigens / immunology*
  • Antigens / metabolism
  • Cell Line
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Endocytosis / immunology
  • Endoplasmic Reticulum / immunology
  • Endoplasmic Reticulum / metabolism
  • Endosomes / immunology
  • Endosomes / metabolism
  • HeLa Cells
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunoblotting
  • Intracellular Space / immunology
  • Intracellular Space / metabolism
  • Microscopy, Confocal
  • Minor Histocompatibility Antigens
  • Protein Binding / immunology
  • Protein Transport / immunology
  • Signal Transduction / immunology*
  • Vitamin B Complex / immunology


  • Antigens
  • Histocompatibility Antigens Class I
  • MR1 protein, human
  • Minor Histocompatibility Antigens
  • Vitamin B Complex