ABSTRACT This proposal is to request support for a Keystone Symposia meeting entitled [unreadable]Lymphocyte Activation and Signaling[unreadable], which will be held in Snowbird, Utah from February 3 [unreadable] 8, 2008. The differentiation and activation of immune cells, including lymphocytes, is tightly controlled by a wide array of signaling molecules. These include receptors sensing external stimuli; kinases and phosphatases controlling the initiation of intracellular biochemical signals; adaptor molecules linking receptors to intracellular effectors; and transcription factors and other genomic modifiers regulating gene expression and structure. Over the past fifteen years, there has been a marked increase in our understanding of the roles and the regulation of these various molecules in a normal immune response. Recently, several of these components have been linked to human diseases such as auto- immunity, immunodeficiencies and lymphoid malignancies. In this symposium, we bring together distinguished researchers working at the cutting edge of immune cell signaling. These scientists will report on their most recent findings and provide a clear picture of where the field is going. The impact of their research findings on a better understanding and, possibly, better treatments of human diseases will be discussed. In particular, this meeting will highlight how immune cells can sense external stimuli and, through intracellular signal transduction cascades, mediate proper biological responses. It will also emphasize the impact of this knowledge on significant clinical problems such as auto-immunity, immunodeficiencies, tumor immunity, transplantation and infectious diseases.