No abstract

We have examined the ability of the CD3-␥␦⑀ and CD3-signaling modules of the T cell receptor (TCR) to couple CD38 to intracellular signaling pathways. The results demonstrated that in TCR ؉ T cells that express the whole set of CD3 subunits CD38 ligation led to complete tyrosine phosphorylation of both CD3-and CD3-⑀ polypeptide chains. In contrast, in TCR ؉ cells with a defective CD3-association CD38 engagement caused tyrosine phosphorylation of CD3-⑀ but not of CD3-. Despite these differences, in both cell types CD38 ligation resulted in protein-tyrosine kinase and mitogen-activated protein kinase activation. However, in cells expressing chimerical CD25-or CD25-⑀ receptors or in a TCR-␤ ؊ Jurkat T cell line, CD38 ligation did not result in tyrosine phosphorylation of the chimeric receptors, or CD3 subunits, or protein-tyrosine kinase or mitogenactivated protein kinase activation. In summary, these results support a model in which CD38 transduces activating signals inside the cell by means of CD3-⑀ and CD3-tyrosine phosphorylation. Moreover, these data identify the CD3-␥␦⑀ signaling module as a necessary and sufficient component of the TCR/CD3 complex involved in T cell activation through CD38.

No abstract