T cell trafficking is critical to immune responses as naïve T cells constantly recirculate into and out of lymph nodes to survey for cognate antigen presented on dendritic cells. While many cell surface receptors including selectins, chemokine receptors, and integrins have been demonstrated to be crucial for T cell motility, less is known about the intracellular mediators of T cell motility. We recently identified PKCθ as a novel regulator of T cell migration. We find that PKCθ deficient T cells show defects in crawling in response to chemokine. In this proposal, we will define the precise role for PKCθ in regulating T cell migration by looking at the motility of T cells directly in intact lymph nodes. We will use quantitative methods to model T cells searching for antigen within lymph nodes through a collaboration with Dr. Melanie Moses of the UNM Computer Science department. We hypothesize that key signaling molecules such as PKCθ contribute to the ability to T cells to search for antigen. We will use a combination of experimental data and modeling to quantify the precise contribution of specific signaling molecules to the ability of T cells to find antigen in lymph nodes.