DIFFERENT CYTOPLASMIC STRUCTURE OF THE CD3-ZETA FAMILY DIMER MODULATES THE ACTIVATION SIGNAL AND FUNCTION OF T-CELLS

The TCR complex transduces the antigen recognition signal through comm on activation motifs present in both CD3 gamma delta epsilon chains an d zeta dimers within the complex. We have investigated functional role s of the cytoplasmic domain in zeta and CD3 gamma delta epsilon for T cell activation in early and late responses by comparing the signaling capability of the TCR complexes containing mutant zeta lacking some o r all motifs, or eta chain, another zeta family molecule. The results with the mutant zeta lacking all motifs indicated that CD3 gamma delta epsilon can transduce signals to cause early activation events and pr oduction of IL-2 upon antigen stimulation in the absence of zeta motif s. However, any one of the zeta motifs was required to respond to Thy- 1 stimulation and this requirement cannot be replaced by other CD3 cha ins. Such zeta motif-dependent responses were also observed in tyrosin e phosphorylation of a 90 kDa protein upon TCR stimulation. Furthermor e, we found that the C-terminal unique region of the eta chain exhibit s inhibitory function in phosphorylation and Ca2+ response upon TCR st imulation as well as IL-2 production upon Thy-1 stimulation. Collectiv ely, the present analyses suggest that two types of signals are induce d through the TCR-CD3 complex: (i) the common motif-dependent signals which are mediated equally through zeta dimers and CD3 gamma delta eps ilon, and (ii) zeta specific motif-dependent signals. Differences in t he cytoplasmic domain of zeta family molecules may modulate the cooper ation of these two signals, resulting in alteration of T cell function s.