A role of kinase inactive ZAP-70 in altered peptide ligand stimulated T cell activation |
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Authors: | Kim Jeong-Ran Irie Atsushi Tsukamoto Hirotake Nishimura Yasuharu |
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Affiliation: | Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Japan. |
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Abstract: | 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. |
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Keywords: | Altered peptide ligand TCR-ζ ZAP-70 Phospholipase Cγ1 T cell activation |
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