Cellular and Molecular Requirements for Extracellular Vesicle-mediated Antigen Delivery to Dendritic Cells – EVUp

Extracellular vesicles (EVs) serve a direct role in intercellular communication by sampling the biochemical content (such as RNAs and proteins) in a donor cell and transferring the sample to an acceptor cell. Little is known of the delivery process of EVs to the recipient cells. This stands in contrast to the translational opportunities that mastering insights into delivery would promise.
EVs have been implicated in multiple physiological functions., including Antigen presentation. Development of adaptive immune responses requires capture of extracellular antigens (Ag) by dendritic cells (DCs), followed by processing, and finally presentation of these antigens on DCs' major histocompatibility Complex (MHC) class I and class II molecules to, respectively, CD8+ and CD4+ T lymphocytes.
We have previously demonstrated that EVs play a significant role in Ag presentation. In addition We also showed that EVs represent a very heterogeneous population, which suggests that specific EV sub-types containing specific cargo may be dedicated to specific acceptor cell type and functions.
We will focus on the mechanism of EV-mediated transfer of Antigen to dendritic cells, because excellent experimental paradigms in this area have been developed, and because the possibility of manipulating the immune response is a high impact translational area.
The present research proposal aims at i) identifying which (if any) EV subtype(s) is/are dedicated to specific acceptor cells and functions (i.e Ag presentation within acceptor Dendritic Cells), ii) identifying the docking and the core fusion machinery that is required for the EV-content delivery within the acceptor cells.