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.
CITATION STYLE
McWilliam, H. E. G., Eckle, S. B. G., Theodossis, A., Liu, L., Chen, Z., Wubben, J. M., … Villadangos, J. A. (2016). The intracellular pathway for the presentation of Vitamin B-related antigens by the antigen-presenting molecule MR1. Nature Immunology, 17(5), 531–537. https://doi.org/10.1038/ni.3416
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