Integrative biology of T cell activation

Nat Immunol. 2014 Sep;15(9):790-7. doi: 10.1038/ni.2959.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology*
  • Humans
  • Lymphocyte Activation / immunology*
  • Membrane Proteins / immunology
  • Receptors, Antigen, T-Cell / immunology*
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*


  • Adaptor Proteins, Signal Transducing
  • Membrane Proteins
  • Receptors, Antigen, T-Cell