TCR zeta chain in T cell development and selection

Current data suggest that an important function of the multimeric structure of the TCR is to enable the assembly of structurally and functionally different forms of the TCR, the pre-TCR and alpha beta TCR complexes, at different stages in development. Four distinct TCR subunits (the CD3 gamma, delta, and epsilon chains and the zeta chain) contain signal transducing motifs; however, the zeta chain is notable for containing three of these elements. These motifs, especially those within the zeta chain, function to amplify signals generated by the TCR, and this property is especially critical during thymocyte selection. The results of several recent experiments argue that positive and negative selection of thymocytes may involve activation of distinct downstream signaling pathways. The outcome of thymocyte selection can also be influenced, however, by quantitative effects such as changes in ligand concentration or direct alteration of the TCR signaling potential. Recent studies pertaining to the kinetics of TCR-ligand interactions may provide insight into how signaling through the TCR can be regulated either quantitatively or qualitatively.