We are interested in understanding the mechanisms by which dendritic cells provoke primary T cell responses in autoimmune diseases such as type-1 diabetes and celiac disease and in pancreatic cancer. We employ transgenic mouse models to decipher the molecular and cellular specializations of dendritic cells that allow these cells to capture, traffic, process and present antigens derived from healthy, developing, and injured tissues. In other studies, we utilize high resolution imaging technologies to investigate the trafficking of antigen and dendritic cells from non-lymphoid organs to draining lymph nodes. We are currently engineering transgenic models in which specific mutations can be targeted to dendritic cells in an inducible manner. Conditional gene targeting in dendritic cells will allow us to more precisely dissect the physiology and function of these critical antigen-presenting cells in health and disease. Elucidating the steps leading to nae T cell activation should provide the necessary framework for enhancing this process in cancer and dampening it in autoimmune diseases.