T cell receptor-mediated signs and signals governing T cell development

The developmental fate of T cells is largely controlled by the nature and success of signals mediated by the pre-T cell receptor (TCR) and TCR complexes. These intracellular signals are regulated by cascades of protein tyrosine phosphorylations initiated following ligand binding to the pre-TCR or TCR complexes. The phosphorylation cascades are primarily orchestrated by two distinct families of protein tyrosine kinases (PTKs), the Src- and the Syk/ZAP-70-families. Germline gene targeting experiments, several human immunodeficiencies, and somatic cell mutants have all contributed to our understanding of how these families of kinases coordinate their actions to promote signaling. Upon activation, the PTKs transmit their signals to a number of newly described adaptor proteins including LAT, SLP-76, and vav, among others. The following review combines results derived from different experimental strategies to examine the contributions of the PTKs and the adaptor molecules to pre-TCR and TCR signaling processes.