Integrative biology of T cell activation.

The activation of T cells mediated by the T cell antigen receptor (TCR) requires the interaction of dozens of proteins, and its malfunction has pathological consequences. Our major focus is on new developments in the systems-level understanding of the TCR signal-transduction network. To make sense of the formidable complexity of this network, we argue that 'fine-grained' methods are needed to assess the relationships among a few components that interact on a nanometric scale, and those should be integrated with high-throughput '-omic' approaches that simultaneously capture large numbers of parameters. We illustrate the utility of this integrative approach with the transmembrane signaling protein Lat, which is a key signaling hub of the TCR signal-transduction network, as a connecting thread.