Lipid peroxidation causes endosomal antigen release for cross-presentation.

Abstract

Dendritic cells (DCs) present foreign antigen in major histocompatibility complex (MHC) class I molecules to cytotoxic T cells in a process called cross-presentation. An important step in this process is the release of antigen from the lumen of endosomes into the cytosol, but the mechanism of this step is still unclear. In this study, we show that reactive oxygen species (ROS) produced by the NADPH-oxidase complex NOX2 cause lipid peroxidation, a membrane disrupting chain-reaction, which in turn results in antigen leakage from endosomes. Antigen leakage and cross-presentation were inhibited by blocking ROS production or scavenging radicals and induced when using a ROS-generating photosensitizer. Endosomal antigen release was impaired in DCs from chronic granulomatous disease (CGD) patients with dysfunctional NOX2. Thus, NOX2 induces antigen release from endosomes for cross-presentation by direct oxidation of endosomal lipids. This constitutes a new cellular function for ROS in regulating immune responses against pathogens and cancer.

DOI: 10.1038/srep22064
010203020162017
Citations per Year

Citation Velocity: 7

Averaging 7 citations per year over the last 2 years.

Learn more about how we calculate this metric in our FAQ.

Cite this paper

@article{Dingjan2016LipidPC, title={Lipid peroxidation causes endosomal antigen release for cross-presentation.}, author={Ilse Dingjan and Dani{\"{e}lle Rj Verboogen and Laurent M Paardekooper and Natalia H Revelo and Simone P Sittig and Linda J Visser and Gabriele Fischer von Mollard and Stefanie Sv Henriet and Carl G Figdor and Martin Ter Beest and Geert van den Bogaart}, journal={Scientific reports}, year={2016}, volume={6}, pages={22064} }