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-zeta and no tyrosine-phosphorylation of zeta-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-zeta. In OPAL-stimulated T cells, PLC-gamma1 was phosphorylated and it was suppressed by DN ZAP-70 expression, suggesting that the ZAP-70-TCR-zeta association mediates the activation of PLC-gamma1 leading to T cell responses even in the absence of kinase activation of ZAP-70.
Kim
Jeong-Ran
JR
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Japan.
Irie
Atsushi
A
Tsukamoto
Hirotake
H
Nishimura
Yasuharu
Y
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000276:immunology*
D008024:Ligands; D010455:Peptides; D051746:ZAP-70 Protein-Tyrosine Kinase