TCR ζ chain in T cell development and selection

Current data suggest that an important function of the multimericstructure of the TCR is to enable the assembly of structurally and functionally different forms of the TCR, the pre-TCR and αβTCR complexes, at different stages in development. Four distinct TCR subunits (the CD3γ, δ, and var epsilon chains and the ζ chain) contain signal transducing motifs; however, the ζ chain is notable for containing three of these elements. These motifs, especially those within the ζ 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.