Characterization of TCR-activated Signaling Complexes and Microclusters

Engagement of the T cell receptor (TCR) results in the formation of microclusters containing many signaling molecules making protein:protein interactions to form signaling complexes. Subsequent signaling events lead to structural rearrangements that produce an immune synapse between the T cell and antigen presenting cell. Microclusters form within seconds of TCR engagement and are the basic signaling units required for T cell activation. However, the key sequence of events by which T lymphocytes establish signaling microclusters remains unclear. To understand the key events that lead to microcluster formation, we imaged the TCR, the transmembrane signaling molecule LAT and many other signaling molecules using super-resolution microscopy. We were able to describe the kinetics of microcluster structure formation. We have extended this work to study the mechanisms by which microcluster formation occurs. In complementary work we have spent many years reconstituting signaling complexes in vitro and have performed biophysical studies to define protein interactions at a molecular level.