Genetic approaches to tyrosine kinase signaling pathways in the immune system.

The development of a productive immune response requires the carefully coordinated activation of lymphocytes through their cell-surface antigen receptors, surface immunoglobulin (Ig) on B cells and the T cell receptor (TCR) on T cells. Studies of mutant cell lines, gene-targeted mice and humans with inherited immunodeficiencies have demonstrated that tyrosine kinases are critical components of lymphocyte antigen-receptor-signaling pathways. Our laboratory is interested in the mechanisms by which modulation of signaling pathways involving tyrosine kinases and related signaling molecules can influence cell function and development. We have concentrated our attention on the genetic and biochemical dissection of signaling pathways in the immune system, and how altering these pathways can change responses to infectious disease. As a model system, we are examining the Tec family kinases and their roles in T lymphocyte development and function.