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VAMP8-mediated NOX2 recruitment to endosomes is necessary for antigen release

Dingjan, I., Paardekooper, L. M., Verboogen, D. R. J., von Mollard, G. F., ter Beest, M. & van den Bogaart, G., Oct-2017, In : European Journal of Cell Biology. 96, 7, p. 705-714 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Ilse Dingjan
  • Laurent M. Paardekooper
  • Danielle R. J. Verboogen
  • Gabriele Fischer von Mollard
  • Martin ter Beest
  • Geert van den Bogaart

Cross-presentation of foreign antigen in major histocompatibility complex (MHC) class I by dendritic cells (DCs) requires activation of the NADPH-oxidase NOX2 complex. We recently showed that NOX2 is recruited to phagosomes by the SNARE protein VAMP8 where NOX2-produced reactive oxygen species (ROS) cause lipid oxidation and membrane disruption, promoting antigen translocation into the cytosol for cross-presentation. In this study, we extend these findings by showing that VAMP8 is also involved in NOX2 trafficking to endosomes. Moreover, we demonstrate in both human and mouse DCs that absence of VAMP8 leads to decreased ROS production, lipid peroxidation and antigen translocation, and that this impairs cross-presentation. In contrast, knockdown of VAMP8 did not affect recruitment of MHC class I and the transporter associated with antigen processing 1 (TAP1) to phagosomes, although surface levels of MHC class I were reduced. Thus, in addition to a secretory role, VAMP8-mediates trafficking of NOX2 to endosomes and phagosomes and this promotes induction of cytolytic T cell immune responses. (C) 2017 The Authors. Published by Elsevier GmbH.

Original languageEnglish
Pages (from-to)705-714
Number of pages10
JournalEuropean Journal of Cell Biology
Volume96
Issue number7
Publication statusPublished - Oct-2017
Externally publishedYes

    Keywords

  • Dendritic cells, VAMPS, NOX2, Cross-presentation, Lipid peroxidation, CONTROLS PHAGOSOMAL PH, HUMAN DENDRITIC CELLS, I CROSS-PRESENTATION, NADPH OXIDASE, PHAGOCYTOSIS, COMPARTMENT, FUSION, CROSSPRESENTATION, EXOCYTOSIS, GRANULES

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