Antigen receptor-mediated phosphoinositide hydrolysis in murine T cells is not initiated via G-protein activation.

Ligation of the antigen receptors on both T and B lymphocytes induces phosphoinositide (PI) hydrolysis, Ca(2+)-mobilization and protein kinase C activation. The activation of the phosphoinositide-specific phosphodiesterase (PPI-PDE) following crosslinking of surface Ig receptors on B cells is controlled by an uncharacterized guanine nucleotide-regulatory (G) protein. Here we have used permeabilized murine T cells (both resting T cells and a conalbumin-specific CD4-positive T cell clone) to investigate a role for G protein(s) in coupling the TCR to the PPI-PDE. We found that anti-TCR McAb (or processed antigen)-induced PI hydrolysis cannot be uncoupled by permeabilizing T cells, as occurs with classical G protein-linked receptors. Furthermore, the TCR-mediated release of inositol phosphates in permeabilized T cells was not enhanced by non-hydrolyzable analogs of GTP, nor inhibited by GDP analogs. These findings therefore argue strongly against the concept that TCR-mediated PI hydrolysis is G-protein controlled.