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

McWilliam, Hamish E G, Eckle, Sidonia B G, Theodossis, Alex, Liu, Ligong, Chen, Zhenjun, Wubben, Jacinta M, Fairlie, David P, Strugnell, Richard A, Mintern, Justine D, McCluskey, James, Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522 and Villadangos, Jose A 2016. The intracellular pathway for the presentation of vitamin B-related antigens by the antigen-presenting molecule MR1. Nature Immunology 10.1038/ni.3416

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Publisher:	Nature Publishing Group
ISSN:	1529-2908
Date of First Compliant Deposit:	10 July 2017
Date of Acceptance:	16 February 2016
Last Modified:	04 May 2023 20:00
URI:	https://orca.cardiff.ac.uk/id/eprint/102234

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