T cell antigen receptor triggered exocytosis in cytotoxic T lymphocytes is inhibited by soluble, but not immobilized monoclonal antibodies to Lyt-2 antigen.
The effect of monoclonal antibodies (mAb) to surface antigens on the T cell antigen receptor (TcR)-triggered exocytosis of intracellular granules in cytotoxic T lymphocytes (CTL) was studied. Soluble anti-LFA-1, anti-TcR, and anti-Lyt-2 mAb inhibited both CTL-inflicted 51Cr-release from the target cell (TC) and TC-stimulated exocytosis of granules from cloned CTL. Soluble anti-TcR and anti-Lyt-2 mAb but not soluble anti-LFA-1 mAb inhibited exocytosis, which was triggered by solid-phase anti-TcR mAb. Immobilized anti-Lyt-2 did not inhibit secretion triggered by immobilized anti-TcR mAb; immobilized anti-LFA-1 mAb had an modest inhibiting effect. Inhibition of exocytosis by soluble anti-Lyt-2 mAb was greater when stimulating anti-TcR mAb were immobilized at a lower density on a plastic surface. When the requirement for TcR cross-linking was bypassed by synergistic action of phorbol ester and ionophore A23187, no inhibition of exocytosis by soluble anti-Lyt-2 mAb was detected. The obtained data point to steric hindrance as the most likely explanation of the inhibition of TcR-triggered CTL activation by anti-Lyt-2 mAb.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D003594:Cytoplasmic Granules / Q000502:physiology; D004950:Esterases / Q000378:metabolism; D005089:Exocytosis; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D004950:Esterases