Scaffolds, adaptors and linkers of TCR signaling: theory and practice

Four non-enzymatic proteins form the structural core of the TCR signaling machinery, linking antigen-receptor activation to signaling. These four proteins, each with well defined protein–protein interaction domains, include three ‘scaffolds’ (LAT, SLP-76 and SLAP-130/Fyb/ADAP and a ‘pure adaptor’ (GADS). The biological functions of many distinct protein–protein interaction domains have been dissected through a methodological series of knockout and reconstitution experiments. In reviewing these recent advances, we attempt to address two questions often asked by immunologists not familiar with the field: what do scaffolds/adaptors/linkers do; and what do these terms mean?