Structural Biology of the T-cell Receptor: Insights into Receptor Assembly, Ligand Recognition, and Initiation of Signaling

Abstract

The T-cell receptor (TCR)-CD3 complex serves as a central paradigm for general principles of receptor assembly, ligand recognition, and signaling in the immune system. There is no other receptor system that matches the diversity of both receptor and ligand components. The recent expansion of the immunological structural database is beginning to identify key principles of MHC and peptide recognition. The multicomponent assembly of the TCR complex illustrates general principles used by many receptors in the immune system, which rely on basic and acidic transmembrane residues to guide assembly. The intrinsic binding of the cytoplasmic domains of the CD3ε and ζ chains to the inner leaflet of the plasma membrane represents a novel mechanism for control of receptor activation: Insertion of critical CD3ε tyrosines into the hydrophobic membrane core prevents their phosphorylation before receptor engagement.