DNGR-1 in DCs · The dendritic cell receptor DNGR-1: Modulation of endosomal dynamics upon recognition of necrotic cells

Dendritic cells (DCs) play an essential function in initiating adaptive immunity. Key to DC function are receptors for recognizing and capturing pathogens and damaged cells and for controlling subsequent antigen extraction, processing and presentation. DNGR-1 (also known as CLEC9A) is a DC-restricted C-type lectin receptor (CLR) that recognizes the actin cytoskeleton exposed on necrotic cells. DNGR-1 is not required for internalization of cell corpses by DCs but regulates their subsequent ability to crosspresent corpse-associated antigens to CD8+ T-cells. The mechanisms underlying DNGR-1 function are unknown but require receptor signaling upon ligand engagement and are though to relate to modulation of endocytic traffic. Here, I hypothesize DNGR-1 promotes the stabilization of a non-degradative endo-/phagosomal compartment containing dead-cell associated cargo to permit antigen extraction from cell corpses and subsequent crosspresentation. I propose to address this hypothesis by investigating the intracellular trafficking of DNGR-1 and its ligand and the role of DNGR-1 on the endo-/phagosomal environment in DCs.