Crosslinking of Fas/CD95 suppresses the CD3-mediated signaling events in Jurkat T cells by inhibiting the association of the T-cell receptor ζ chain with src-protein tyrosine kinases and ZAP70

摘要: Crosslinking of Fas (APO-1/CD95) on the surface T cells initiates a biochemical cascade leading to programmed cell death. We have previously shown that crosslinking with an apoptosis-inducing IgM anti-Fas mAb results in suppression CD3-initiated signaling including Ca2+ mobilization and protein tyrosine phosphorylation. conducted experiments decipher mechanisms whereby cross talk between Fas- CD3 pathways occur. used lysates from Jurkat examined composition TCR ζ chain-precipitated immune complexes using immunoblots. While affected association p59fyn p56lck kinases chain limited degree, it dramatically inhibited kinase ZAP70 chain. In were preincubated mAb, binding phosphatases SHP-1 was increased. These indicate interferes early events by promoting recruitment decreasing Therefore, antigen may regulate antigen-induced response play active role anergy.