Triggering of the phosphoinositide transduction pathway by a monoclonal antibody specific for the human γ/δ T cell receptor

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Abstract
We have developed a monoclonal antibody (mAb), termed anti-TigammaA, which recognizes an antigenic determinant carried by a variable segment of the T cell receptor (TcR) γ chain. This determinant, encoded by the Vγ9 gene, is expressed on approximately 3% of peripheral blood lymphocytes. In the present study, we have found that binding of anti-TigammaA mAb to its specific ligand results in the triggering of the phosphatidylinositol (PI) cycle-related metabolic process. Indeed, an increased labeling of both phosphatidic acid and PI, related to an enhanced turnover of PI cycle-dependent phospholipids, was observed following exposure of 32P orthophosphoric acid-labeled cells to anti-TigammaA mAb. In addition, there was a rapid rise in intracellular free calcium concentrations. Similar experiments have been performed previously on CD3+ TcRα/β−-cells with an anti-CD3 mAB. They predicted that signals produced by the interaction between the second TcR and its ligand(s) would be transmitted via the PI cycle-linked intracellular second messengers. We confirm this hypothesis in an experimental system where stimulation occurs directly through the γ/δ receptor structure.

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