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 common activation motifs present in both CD3 gamma delta epsilon chains and zeta dimers within the complex. We have investigated functional roles 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 or 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 production of IL-2 upon antigen stimulation in the absence of zeta motifs. However, any one of the zeta motifs was required to respond to Thy-1 stimulation and this requirement cannot be replaced by other CD3 chains. Such zeta motif-dependent responses were also observed in tyrosine phosphorylation of a 90 kDa protein upon TCR stimulation. Furthermore, we found that the C-terminal unique region of the eta chain exhibits inhibitory function in phosphorylation and Ca2+ response upon TCR stimulation as well as IL-2 production upon Thy-1 stimulation. Collectively, the present analyses suggest that two types of signals are induced through the TCR-CD3 complex: (i) the common motif-dependent signals which are mediated equally through zeta dimers and CD3 gamma delta epsilon, and (ii) zeta specific motif-dependent signals. Differences in the cytoplasmic domain of zeta family molecules may modulate the cooperation of these two signals, resulting in alteration of T cell functions.
Aoe
T
T
Division of Molecular Genetics, Chiba University, School of Medicine, Japan.
Goto
S
S
Ohno
H
H
Saito
T
T
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D004247:DNA / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D007295:Inositol Phosphates / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D007295:Inositol Phosphates; D007376:Interleukin-2; D008565:Membrane Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D004247:DNA; D002118:Calcium