The small GTPase Rab22a controls the intracellular trafficking of MHC class I molecules and antigen cross presentation by dendritic cells

IGNACIO CEBRIÁN; CRISTINA CROCE; NICOLAS BLANCHARD; LUIS MAYORGA

Buenos Aires

Congreso; 1st LASID - SAI - FAIC Meeting; 2015

Sociedad Argentina de Inmunología

BackgroundCross presentation is characterized for the processing and presentation of exogenous antigens to class I molecules of the major histocompatibility complex (MHC) to activate CD8+ T lymphocytes. This process has been shown to be crucial for initiating cytotoxic immune responses against diverse pathogens and tumors cells. In this context, dendritic cells (DCs) have developed strong specializations of their endocytic pathway to be the most adapted antigen presenting cells to perform efficiently cross presentation. Methods and ResultsIn this study, we identify the GTPase Rab22a as a key regulator of the intracellular trafficking of MHC-I molecules in DCs. By the use of immunofluorescence techniques and confocal microscopy we show that Rab22a localizes to different endocytic compartments and that it is early recruited to DC endosomes and phagosomes, as well as to the Toxoplasma gondii containing vacuole. Rab22a recruitment to DC phagosomes was further confirmed by biochemical purification and western blot analysis. Upon silencing Rab22a expression in DCs, the trafficking of MHC-I molecules is drastically altered and the cross presentation capacity is compromised after endocytosis of soluble ovalbumin (OVA) or T. gondii infection. However, neither the recruitment of MHC-I molecules to DC phagosomes nor the uptake of exogenous antigens follows a Rab22a-dependent mechanism. ConclusionsAltogether, our findings highlight the critical relevance of the endocytic network in DCs for the trafficking of exogenous antigens during cross presentation through recycling and sorting compartments.