title: Role of phosphatidylinositol-anchored proteins in T cell activation.
abstract: A novel class of cell surface proteins are attached to the plasma membrane via a phosphatidylinositol (PI)-glycan anchoring structure, and these proteins can be selectively removed from the cell surface by the enzyme PI-specific phospholipase C (PI-PLC). Enzyme treatment led to a prolonged reduction in cell surface expression of several PI-anchored proteins. Activation of T cells led to a marked decrease in the ability of PI-PLC to remove PI-anchored surface proteins from the activated T cells. This decrease in PI-PLC sensitivity may reflect an alteration in the PI-glycan anchoring structures, or in a general membrane property, which renders the PI-anchored proteins inaccessible to the enzyme. When murine T lymphocytes were treated with PI-PLC and then stimulated with either Con A, the calcium ionophore A23187 and PMA, or an anti-CD3 mAb, the response to Con A stimulation was inhibited by 90%, whereas the responses to ionophore and PMA or anti-CD3 were not affected. Removal of PI-anchored proteins inhibited an early event in the activation process in response to Con A because both IL-2 production and IL-2R expression were inhibited by the PI-PLC treatment. Inhibition of the Con A response was secondary to removal of a PI-linked protein from the responder T cell population because PI-PLC treatment of T-depleted spleen cells did not alter their ability to act as a source of accessory cells. It is unlikely that removal of the known PI-linked proteins on murine T cells, Thy-1 and Ly-6, can fully account for the inhibition of Con A response because the cell line M2B3, that lacks these surface proteins, responded normally to Con A stimulation. These studies demonstrate that one or more PI-anchored T cell proteins play an important role in an early step of Con A activation, perhaps involving T cell-accessory cell interactions. In contrast, the ability to stimulate T cells by direct cross-linking of TCR/CD3 complex is not dependent on the presence of these PI-anchored proteins.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
authors.forename: D H
authors.initials: DH
authors.lastname: Presky
authors.forename: M G
authors.initials: MG
authors.lastname: Low
authors.forename: E M
authors.initials: EM
authors.lastname: Shevach
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000950:Antigens, Ly / Q000502:physiology; D000954:Antigens, Surface / Q000032:analysis / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D017261:Glycosylphosphatidylinositols; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000502:physiology*; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D011134:Polysaccharides / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018800:Thy-1 Antigens
chemical_list: D000950:Antigens, Ly; D000954:Antigens, Surface; D017261:Glycosylphosphatidylinositols; D010716:Phosphatidylinositols; D011134:Polysaccharides; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D003208:Concanavalin A; D000001:Calcimycin; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D013755:Tetradecanoylphorbol Acetate