Growth arrest of γδ T cells induced by monoclonal antibody against WC1 correlates with activation of multiple tyrosine phosphatases and dephosphorylation of MAP kinase erk2

摘要

AbstractWC1 is a 215‐kDa type 1 transmembrane glycoprotein, the expression of which is restricted to γδ T lymphocytes. The binding of an anti‐WC1 monoclonal antibody (mAb) (SC‐29) induces reversible growth arrest in proliferating interleukin (IL)‐2‐dependent γδ T lymphocytes and this study has examined the relevant biochemical mechanisms. WC1 binding activates multiple protein tyrosine phosphatases causing specific tyrosine dephosphorylation in the absence of calcium mobilization. One of the dephosphorylated proteins was identified as the MAP kinase erk2. Another phosphotyrosine protein of 70 kDa, found to coprecipitate with p85 phosphoinositol (PI)3‐kinase was either dephosphorylated or uncoupled from the p85 PI 3‐kinase immunoprecipitate after WC1 receptor binding by mAb SC‐29. The anti‐WC1‐induced tyrosine dephosphorylation was reversed by stimulation of γδ T cells with concanavalin A or anti‐CD3 mAb, demonstrating that at the biochemical level, mitogen stimulation is dominant to the growth‐arresting effects of anti‐WC1. It is therefore proposed that the activation of tyrosine phosphatases by WC1 binding and the resultant dephosphorylation of certain key signaling protein such as erk2 correlates with and may cause the induction of growth arrest in IL‐2‐dependent γδ T cells, without affecting the cells ability to respond to antigen. Possible mechanisms, which include the inhibition of IL‐2 sign