Phagosome maturation during antigen cross presentation in dendritic cells

IGNACIO CEBRIAN; LUIS MAYORGA

Yokohama

Taller; RCAI International Summer Program (RISP) 2013; 2013

RIKEN

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 only antigen presenting cells that can perform efficiently antigen cross presentation, and this process has been involved in establishing cytotoxic immune responses against bacteria, tumors and certain virus that do not infect DCs. Many features of the intracellular pathways used for the cross presentations process have been elucidated in the past ten years, for instance the existence of two general pathways. One called the vacuolar pathway, which is proteasome-independent and the other one called the cytosolic pathway, which is proteasome-dependent. This second, considered to be the most relevant for cross presentation, implies a tight regulation of the phagosomal pH and membrane fusion events between ER-derived vesicles with phagosomes, among other important points. Nevertheless, many other questions still remain without an answer. One of these unsolved issues is to determine how the peptides derived from the exogenous antigens are loaded into MHC-I molecules. If the antigenic peptides are associated with MHC-I molecules in the classical secretory pathway or directly inside the phagosome it is not known. We consider that recycling compartments may be having an important role in this step of antigen cross presentation by modulating phagosome maturation and the trafficking of MHC-I molecules. To deepen into this idea, we focus our present project on Rab proteins which are key mediators of all membrane trafficking events inside the cell. Indeed, we found that Rab22a, a molecule already proposed to be involved in mediating the recycling of MHC-I molecules, is recruited to DC phagosomes very early after latex beads internalization. Further experimental work will help us to understand a more precise role of this protein in the modulation of phagosome maturation and the presentation of exogenous antigens in the context of MHC-I molecules.