How Rab27a contributes to antigen presentation in dendritic cells

JANCIC, CAROLINA; SAVINA, ARIEL; WASMEIER, CHRISTINA; SEABRA, MIGUEL; RAPOSO, GRAÇA; AMIGORENA, SEBASTIÁN

Paris

Simposio; Réunion parisienne du Club Exocytose-Endocytose. Du trafic à la pathologie, application aux cellules neuronales et immunologiques; 2007

To prevent excessive degradation of internalized antigens, which could destroy the peptides recognized by T lymphocytes, dendritic cells have developed several trategies that limit proteolytic activity in phagosomes. The recruitment of the NADPH oxidase NOX2 prevents acidification of phagosomes, limiting antigen degradation. Here, we show that dendritic cells derived from Rab27a-deficient ashen mice show increased phagosome acidification and antigen degradation, causing a defect in antigen cross-presentation. Enhanced acidification results from a delay in the recruitment to phagosomes of a subset of lysosome-related organelles containing the membrane subunits of NOX2. The Rab27a-dependent recruitment of these "inhibitory lysosomerelated organelles" to phagosomes continuously limits acidification and degradation of ingested particles in dendritic cells, thus promoting antigen cross-presentation.