Modeling the effect of PKCθ on T cell motility in lymph nodes (P5192)

Abstract

Abstract The adaptive immune response is an integrated process that requires the interaction of T lymphocytes and antigen-presenting cells (dendritic cells) within the context of lymph nodes. Under homeostatic conditions, T lymphocytes actively “scan” the lymph node cortex, interacting with multiple dendritic cells (DCs) in search of cognate antigen. T cell motility is driven by CCR7-CCL21/19 and this chemokine-driven motility dictates the rate of interaction between T cells and DCs in lymph nodes and sets the properties of T cell - dendritic cell encounters. We recently found that CCR7 signaling alone without T cell receptor stimulation can activate PKCθ in naïve T cells. Using 2-photon imaging as well as in vitro migration assays, we show that PKCθ is required for optimal T cell migration. We have now generated a computer model to recapitulate the motility of both wild type and PKCθ-deficient T cells in the lymph node. By comparing the behavior of WT versus PKCθ-deficient T cells in our model, we will be able to determine whether the absence of PKCθ compromises interactions between T cells and dendritic cells in the lymph nodes, and therefore the initiation of an adaptive immune response. Our model will allow us to test not only the role for PKCθ in regulating T cell search for antigen, but also the role for other signaling molecules that may regulate T cell motility in vivo.