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The response of lymphocytes to antigen represents a unique opportunity to study how complex molecular interactions between cells lead to developmental decisions, differentiation and proliferation. We'd like to understand how antigen receptors initiate signal transduction events. Antigen receptors functionally interact with tyrosine kinases and phosphatases, enzymes that regulate protein phosphorylation. We are using genetically selective small molecule inhibitors of kinases together with phosphatase mutants to study how thresholds for the initiation of immune responses are set and how feedback circuits influence responses. Our goal is to understand how these pathways control cellular responses in in normal and pathological immune responses.