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

Hamish E G McWilliam, Sidonia B G Eckle, Alex Theodossis, Ligong Liu, Zhenjun Chen, Jacinta M Wubben, David P Fairlie, Richard A Strugnell, Justine D Mintern, James McCluskey, Jamie Rossjohn, Jose A Villadangos

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Pages (from-to)531-537
Number of pages7
JournalNature Immunology
Volume17
Issue number5
DOIs
Publication statusPublished - May 2016

Keywords

  • antigen processing and presentation
  • innate immune cells

Cite this

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
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 ; Villadangos, Jose A. / The intracellular pathway for the presentation of vitamin B-related antigens by the antigen-presenting molecule MR1. In: Nature Immunology. 2016 ; Vol. 17, No. 5. pp. 531-537.
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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.",
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McWilliam, HEG, Eckle, SBG, Theodossis, A, Liu, L, Chen, Z, Wubben, JM, Fairlie, DP, Strugnell, RA, Mintern, JD, McCluskey, J, Rossjohn, J & Villadangos, JA 2016, 'The intracellular pathway for the presentation of vitamin B-related antigens by the antigen-presenting molecule MR1' Nature Immunology, vol. 17, no. 5, pp. 531-537. https://doi.org/10.1038/ni.3416

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; Villadangos, Jose A.

In: Nature Immunology, Vol. 17, No. 5, 05.2016, p. 531-537.

Research output: Contribution to journalArticleResearchpeer-review

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