New insights into the T cell synapse from single molecule techniques.

T cell activation depends on extracellular ligation of the T cell receptor (TCR) by peptide-MHC complexes in a synapse between the T cell and an antigen-presenting cell. The process then requires the assembly of signalling complexes between the TCR and the adaptor protein linker for activation of T cells (LAT), and subsequent filamentous actin (F-actin)-dependent TCR cluster formation. Recent progress in each of these areas, made possible by the emergence of new techniques, has forced us to rethink our assumptions and consider some radical new models. These describe the receptor interaction parameters that control T cell responses and the mechanism by which LAT is recruited to the TCR signalling machinery. This is an exciting time in T cell biology, and further innovation in imaging and genomics is likely to lead to a greater understanding of how T cells are activated.