Disruption of key GTPase regulators of endocytic recycling compartment does not interfere with soluble antigen crosspresentation in dendritic cells.

Abstract

Crosspresentation is of vital significance to immune surveillance. External antigens, soluble or solid, enter cells via endophagocytic vesicles and are eventually delivered to MHC class I molecules on the cell surface. After antigen uptake, there are three proposed pathways leading to surface MHC class I/peptide complex presentation. Direct translocation into the cytosol to use the conventional proteasome/TAP-dependent ER peptide loading; phagosome autonomous presentation following fusion with selected ER components; and endocytic recycling whereby antigens are processed within the endosome and form a complex with internalized MHC class I, for redelivery back to cell surface.1 Endocytic recycling compartment (ERC), a major perinuclear tubular network considered critical for slow endosomal recycling, has been suggested to be one route for crosspresentation.2 This pathway is particularly relevant for soluble antigen presentation, as the former two routes are mostly used to describe particulate antigen processing, involving phagosomes. Here we report the unexpected finding that disruption of key regulatory factors of ERC, small GTPase proteins ARF6, Rab11a, and Rab22a, had no effect on soluble ovalbumin (OVA) crosspresentation in a model dendritic cell system.