Selected signalling proteins recruited to the T-cell receptor-CD3 complex

Summary The T-cell receptor (TCR)–CD3 complex, expressed on T cells, determines the outcome of a T-cell response. It consists of the TCR-αβ heterodimer and the non-covalently associated signalling dimers of CD3eγ, CD3eδ and CD3ζζ. TCR-αβ binds specifically to a cognate peptide antigen bound to an MHC molecule, whereas the CD3 subunits transmit the signal into the cytosol to activate signalling events. Recruitment of proteins to specialized localizations is one mechanism to regulate activation and termination of signalling. In the last 25 years a large number of signalling molecules recruited to the TCR–CD3 complex upon antigen binding to TCR-αβ have been described. Here, we review knowledge about five of those interaction partners: Lck, ZAP-70, Nck, WASP and Numb. Some of these proteins have been targeted in the development of immunomodulatory drugs aiming to treat patients with autoimmune diseases and organ transplants.