The immunological synapse: required for T cell receptor signalling or directing T cell effector function?

The discovery of the immunological synapse is one of the more striking developments in T cell biology in recent years. The immunological synapse forms at the interface between T cells and antigen-presenting cells (APCs) or target cells. It is characterised by the large-scale segregation of cell surface molecules into concentric zones, forming a bull's eye pattern several microns in diameter (reviewed in [1]). In their excellent review of recent work on the immunological synapse, published in Current Biology [2], Delon and Germain correctly stress, as we have [1], that synapse formation follows, and is dependent on, T cell antigen receptor (TCR) signalling. Although this indicates that synapse formation is not required for TCR signalling, they nevertheless conclude, as have others [3], that a principal function of the synapse is to " stabilise signal transduction by the TCR for the prolonged periods of time required for gene activation " [2]. As we discuss below, recent work suggests that the dynamics of TCR signalling are likely to be profoundly altered by synapse formation. Rather than being important for TCR signalling, we argue that immunological synapse formation is linked instead to the delivery of secondary T cell signalling and effector functions, such as directed secretion. The protein kinase p56lck,