Trichosanthin inhibits T cell activation by interfering with the recruitment of ZAP-70 to CD3 zeta chain.
Plant protein Trichosanthin (Tk) has been shown in our previous experiments to suppress antigenic response of T cells. Here we explored its inhibitory mechanisms on the proliferation of human Jurkat leukemia T cell triggered by anti-CD3 McAb. By examination of tyrosine phosphorylation of cell lysate, we were able to show that Tk could interfere with the PTK-related activity in the TCR/CD3-initiated signal transduction in addition to blocking the phosphorylation of PKC. As shown in our experiment, the expression intensity of ZAP-70, a kind of protein tyrosine kinase, was not changed but its phosphorylation could be inhibited. When physical link between CD3 zeta chain and ZAP-70 was further examined by using coimmunoprecipitation after pluse-treatment of the cell line with Tk, the anti-CD3 McAb-induced recruitment of ZAP-70 to CD3 zeta chain was observed to be blocked in some extent. This may account for, at least in part, how Trichosanthin was able to inhibit the TCR-triggered T cell proliferation.
Hong
J
J
Shanghai Institute of Immunology, Shanghai Second Medical University, China.
Fu
S L
SL
Shen
Z Y
ZY
Lu
P H
PH
Chou
K Y
KY
D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017252:CD3 Complex / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015978:Trichosanthin / Q000494:pharmacology*; D051746:ZAP-70 Protein-Tyrosine Kinase
D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D017252:CD3 Complex; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D019000:Phosphotyrosine; D015978:Trichosanthin; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human