Characterization of signaling complexes at the T-cell antigen receptor

Engagement of the T-cell antigen receptor (TCR) induces the assembly of signaling complexes comprised of adapter molecules and enzymes. We use multiple approaches in our characterization of these complexes and the process of signal transduction mediated by the TCR. Our genetic approach is the study of mutations in a critical adapter molecule, LAT. Some of these mutations lead to an interesting lympho-proliferative disorder. Signaling complexes can be studied in vitro using biochemical and biophysical methods to determine the rules of signal complex formation. Finally, we visualize the formation and fate of multi-protein complexes at the site of TCR activation. To do so, we express various fluorescently-tagged signaling proteins in T cells and observe clusters of molecules containing the TCR and important adapters and enzymes. Direct imaging of signaling molecules has revealed the highly dynamic nature of molecular interactions at the TCR.