Journal article
The intracellular pathway for the presentation of Vitamin B-related antigens by the antigen-presenting molecule MR1
HEG McWilliam, SBG Eckle, A Theodossis, L Liu, Z Chen, JM Wubben, DP Fairlie, RA Strugnell, JD Mintern, J McCluskey, J Rossjohn, JA Villadangos
Nature Immunology | Published : 2016
DOI: 10.1038/ni.3416
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, althoug..
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Funding Acknowledgements
We thank T. Hansen (University of Washington) and W.J. Yankelevich (US Food and Drug Administration) for the gift of the 8F2.F9 hybridoma; L. Knodler (Washington State University College) for mCherry reagents; C. Dumont (University of Melbourne) for assistance with the internalization and recycling assays; H. Reid (Monash University) for assistance in cloning the MR1 K43R mutant; S. Londrigan (University of Melbourne) for assistance with the bronchial epithelial cells; and the Biological Optical Microscopy Platform (University of Melbourne) for microscopy expertise. S.B.G.E. is supported by an Early Career Research award from The University of Melbourne. This research was supported by the Australian National Health and Medical Research Council (NHMRC) (D.P.F., R.A.S., J.M., J.R. and J.A.V.) and the Australian Research Council (D.P.F. and J.R.).