A role of kinase inactive ZAP-70 in altered peptide ligand stimulated T cell activation

T cell activation signals induced by altered peptide ligands (APLs) are different from those induced by the original agonistic peptide. The characteristics of the former are partial phosphorylation of TCR-ζ and no tyrosine-phosphorylation of ζ-associated protein-70 (ZAP-70). To analyze further those signaling pathways, we introduced a dominant negative (DN) form of ZAP-70 into a human CD4+ T cell clone in which fully and partially agonistic peptide ligands have been well characterized. We found that some over-expressed partially agonistic ligands (OPALs) induced T cell responses without tyrosine-phosphorylation and kinase activation of ZAP-70. However, those responses were inhibited in T cells expressing DN ZAP-70, which could associate with partially phosphorylated TCR-ζ. In OPAL-stimulated T cells, PLC-γ1 was phosphorylated and it was suppressed by DN ZAP-70 expression, suggesting that the ZAP-70-TCR-ζ association mediates the activation of PLC-γ1 leading to T cell responses even in the absence of kinase activation of ZAP-70.