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

Hamish E G McWilliam, Sidonia B G Eckle, Alex Theodossis, Ligong Liu, Zhenjun Chen, Jacinta M Wubben, David P Fairlie, Richard A Strugnell, Justine D Mintern, James McCluskey, Jamie Rossjohn, Jose A Villadangos

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Abstract

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.
Original languageEnglish
Pages (from-to)531-537
Number of pages7
JournalNature Immunology
Volume17
Issue number5
DOIs
Publication statusPublished - May 2016

Keywords

  • antigen processing and presentation
  • innate immune cells

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