title: The intracellular pathway for the presentation of vitamin B-related antigens by the antigen-presenting molecule MR1.
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.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia.|Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.|Australian Research Council (ARC) Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
authors.forename: Hamish E G
authors.initials: HE
authors.lastname: McWilliam
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
authors.forename: Sidonia B G
authors.identifier: http://orcid.org/0000-0003-0766-171X
authors.initials: SB
authors.lastname: Eckle
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Theodossis
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.|ARC Centre of Excellence in Advanced Molecular Imaging, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Ligong
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.|Australian Research Council (ARC) Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
authors.forename: Jacinta M
authors.initials: JM
authors.lastname: Wubben
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.|ARC Centre of Excellence in Advanced Molecular Imaging, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
authors.forename: Richard A
authors.identifier: http://orcid.org/0000-0003-0614-5641
authors.initials: RA
authors.lastname: Strugnell
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Justine D
authors.initials: JD
authors.lastname: Mintern
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.|Australian Research Council (ARC) Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.|Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia.|Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Villadangos
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004705:Endocytosis / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D042541:Intracellular Space / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D015778:Minor Histocompatibility Antigens; D011485:Protein Binding / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D014803:Vitamin B Complex / Q000276:immunology
chemical_list: D000941:Antigens; D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D014803:Vitamin B Complex