Molecular interactions at the T cell–antigen-presenting cell interface

The development of new imaging techniques has made it possible to investigate the dynamic movements of molecules involved in T-cell signalling. Fluorescence resonance energy transfer (FRET) imaging allows the investigation of protein–protein interactions in live cells, and has demonstrated that T-cell receptors (TCRs) and CD4 are brought together in the immunological synapse during antigen recognition. This interaction is inhibited by antagonist ligands. Antagonism works through competition between agonist and antagonist ligands for TCR binding, as well as through feedback via the SHP-1 tyrosine phosphatase and extracellular signal-related kinase. Early signalling events result in the clustering of co-receptors and TCRs at the synapse, and the activation of various signalling molecules. Recent data show that some T-cell signalling precedes the formation of the mature form of the immunological synapse, but that full T-cell activation depends on sustained signalling, which in turn requires the synapse.