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

Autor: McWilliam HE; 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., Eckle SB; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia., Theodossis A; Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Liu L; 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., Chen Z; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia., Wubben JM; 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., Fairlie DP; 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., Strugnell RA; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia., Mintern JD; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia., McCluskey J; Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia., Rossjohn J; 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., Villadangos JA; 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.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2016 May; Vol. 17 (5), pp. 531-7. Date of Electronic Publication: 2016 Apr 04.
DOI: 10.1038/ni.3416
Abstrakt: 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.
Databáze: MEDLINE
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