REGULAR ARTICLES
Cell Research (1998)8:33-39
© 1998 SIBS, CAS All rights reserved 1001-0602/98
Trichosanthin inhibits T cell activation by interfering with
the recruitment of ZAP-70 to CD3 zeta chain.
Hong J, Fu SL, Shen ZY, Lu PH, Chou KY.
Shanghai Institute of Immunology, Shanghai Second Medical University,
China
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.
Keywords : Trichosanthin;
TCR signaling; PTK; tyrosine phosphorylation. |