Triggering of the phosphoinositide transduction pathway by a monoclonal antibody specific for the human gamma/delta T cell receptor.
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) gamma chain. This determinant, encoded by the V gamma 9 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+ TcR alpha/beta- -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 gamma/delta receptor structure.
Bismuth
G
G
Laboratoire d'Immunologie Cellulaire et Tissulaire, Hospitalo-Universitaire Pitié, Salpétrière, Paris, France.
Faure
F
F
Theodorou
I
I
Debré
P
P
Hercend
T
T
D000911:Antibodies, Monoclonal / Q000276:immunology; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D003593:Cytoplasm / Q000502:physiology; D006801:Humans; D007158:Immunologic Techniques; D008213:Lymphocyte Activation; D010712:Phosphatidic Acids / Q000502:physiology; D010716:Phosphatidylinositols / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D002118:Calcium