Project 3 Outline

This treatment exploits the cross-presentation function of the immune system that allows antigen-presenting cells (APCs), especially dendritic cells (DCs) to phagocytose extracellular antigens and display them with MHC class I molecules to CD8+ T cells. Typically, extracellular antigens are phagocytosed by APCs and presented through MHC class II to CD4+ T cells, while endogenous antigens are presented through MHC class I to CD8+ T cells. This ability to display extracellular (vaccine-injected) TAAs on MHC I is crucial in the activation of CD8+ T cells in killing the tumor. There are currently two routes for this mechanism of cross-presentation: cytosolic and vacuolar (Immune Response 2014). In the cytosolic route, the extracellular antigen is phagocytosed and then actively transported to the cytosol, where it is cleaved by a proteasome, transported to the ER, and loaded onto MHC class I. In the vacuolar route, the extracellular antigen is phagocytosed and then at the ER is incorporated into an early endosome with lysosomal enzymes and MHC class I, which subsequently displays the antigen on the plasma membrane (Immune Response 2014). The specific pathways involving cross-presentation remain unclear to me and requires further research. I also need to look into mechanisms of APC function, especially those of dendritic cells, so the cancer vaccine treatment will be able to work properly.