Rab27a plays a critical role in antigen cross presentation in dendritic cells

JANCIC, CAROLINA; SAVINA, ARIEL; WASMEIER, CHRISTINA; GUERMONPREZ, PIERRE; VARGAS, PABLO; MOURA, IVÁN; LENNON-DUMENIL, ANA MARÍA; SEABRA, MIGUEL; RAPOSO, GRAÇA; AMIGORENA, SEBASTIÁN

Toulouse

Congreso; Congrès Annuel de la Société Française d'Immunologie et Club Francophone de Cellules Dendritiques; 2005

To initiate cytotoxic immune responses and maintain peripheral tolerance to self, dendritic cells (DCs) must present phagocytosed antigens to CD8+ T lymphocytes, a process called ?cross presentation?. Cross presentation requires regulated proteolysis of antigens into large fragments which are then exported into the cytosol for further processing. After proteosome degradation peptides are translocated into specialized ER-phagosomes compartments and loaded onto MHC class I molecules. We now show that ashen DCs, which are defective for the small GTPase Rab27a, fail to cross present efficiently the model antigen ovalbumin (OVA) to CD8+ OVA-specific T cell hybrids. When we analyzed the efficiency of OVA degradation we found that it was around  two-fold higher in ashen phagosomes compare to wt. To confirm that the defect in cross presentation in ashen DCs was due to an increase in protein degradation, we use ammonium chloride or a cocktail of proteases inhibitors. Cross presentation in ashen DC was recovered to wt levels when protein degradation was partially blocked. We conclude that Rab27a expression is required for maintaining a low proteolytic environment in phagosomes of DCs, which favors cross presentation.