The T Cell Receptor: Critical Role of the Membrane Environment in Receptor Assembly and Function

Recent studies have demonstrated that cell membranes provide a unique environment for protein-protein and protein-lipid interactions that are critical for the assembly and function of the T cell receptor (TCR)-CD3 complex. Highly specific polar interactions among transmembrane (TM) domains that are uniquely favorable in the lipid environment organize the association of the three signaling dimers with the TCR. Each of these three assembly steps depends on the formation of a three-helix interface between one basic and two acidic residues in the membrane environment. The same polar TM residues that drive assembly also play a central role in quality control and export by directing the retention and degradation of free subunits and partial complexes, while membrane proximal cytoplasmic signals control recycling and degradation of surface receptors. Recent studies also suggest that interactions between the membrane and the cytoplasmic domains of CD3 proteins may be important for receptor triggering.