Role of the GTPase Rab22a during antigen cross presentation by dendritic cells

IGNACIO CEBRIAN; LUIS MAYORGA

Rosario

Congreso; SAIB 2014 - 50th Annual Meeting; 2014

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Cross presentation is the process by which exogenous antigens are processed and presented to the class I molecules of histocompatibility complex (MHC) to activate a CD8+ T cell response. Dendritic cells (DCs) have been shown to be the most adapted antigen presenting cells to perform efficiently cross presentation. To do this, DCs have developed a strong specialization of their internalization pathway and many of the intracellular features used for cross presentation have been elucidated. Nevertheless several open questions remain unclear, for instance to determine how the peptides derived from exogenous antigens are loaded into MHC-I molecules. We consider that recycling compartments may be having an important role in this step of cross presentation by modulating the trafficking of MHC-I molecules. So, we focus our study on Rab22a, a GTPase already proposed to be involved in mediating the recycling of MHC-I molecules. We found that this protein localizes to recycling compartments in DCs and is recruited to phagosomes very early after latex beads internalization. After silencing the expression of Rab22a, DCs fail to cross present antigens efficiently and this defect cannot be explained by a lack of MHC-I molecules expression. These results evidence a critical role for Rab22a in antigen cross presentation and point it out as a potential target for immunotherapy.