REQUIREMENTS FOR DIFFERENTIATION OF AN IMMATURE CD4(-CELL LINE()8(+) T)

The CD3 epsilon and zeta chains of the TCR have been shown to possess independent signaling capabilities. Studies with chimeric molecules co ntaining the cytoplasmic domains of either zeta or epsilon have sugges ted that these two structurally distinct members of the TCR-CD3 comple x are able to function autonomously and have redundant features in the context of TCR-signal transduction in mature T cells. Expression of a chimeric human IL-2-receptor-zeta-chain molecule in the CD4(+)8(+) T- cell line, DPK, has enabled us to directly analyze responses initiated by the zeta-chain-signaling module alone within the context of immatu re T-cell differentiation. In this paper, we show that antibody crossl inking of the chimeric zeta chain delivers only a limited activation s ignal as measured by Ca[2(+)] flux, induction of low-level CD5 express ion, and minimal differentiation as assessed by loss of cell-surface C D8 expression. TCR-induced activation through antibody crosslinking of the endogenous CD3 epsilon receptor in the absence of costimulation w as also relatively inefficient in initiating activation and differenti ation. However, co-crosslinking of the CD4 coreceptor with CD3 resulte d in a synergistic response, where as there was little effect of co-cr osslinking of CD4 and the zeta-chain chimera. Striking differences wer e also observed in the substrate pattern of tyrosine phosphorylation, as well as lymphokine secretion following triggering through the intac t TCR Versus the zeta chain alone. These results indicate that althoug h the zeta-chain may possess some signaling capacities similar to that of the intact TCR, it appears to have limited function as an autonomo us subunit in initiating CD4(+)8(+) T-cell differentiation.