TAP transcription and phosphatidylinositol linkage mutants are defective in activation through the T cell receptor.
TAP is a phosphatidylinositol-anchored membrane protein that is involved in murine T lymphocyte activation. To determine the relationship between TAP and T cell receptor/CD3-mediated activation, we derived TAP expression mutants of a T-T hybridoma. Two phenotypically distinct classes of mutants were obtained. The first has a selective defect in the transcription of TAP, while the second has a defect in the biosynthesis of phosphatidylinositol-protein linkages. Both mutations affect antigen-stimulated, T cell receptor-mediated activation of the T-T hybrid. These variants have intact immune effector gene programs, as they are responsive to pharmacologic agents that mimic receptor signals. These findings support a role for phosphatidylinositol-linked cell-surface glycoproteins in physiologic T cell activation. Consistent with this interpretation, we observed similar defects in T cell responsiveness after enzymatic removal of phosphatidylinositol-linked proteins from normal T lymphocytes.
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics* / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002999:Clone Cells / Q000276:immunology; D007163:Immunosorbent Techniques; D008213:Lymphocyte Activation; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009693:Nucleic Acid Hybridization; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018800:Thy-1 Antigens; D014158:Transcription, Genetic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000954:Antigens, Surface; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D018800:Thy-1 Antigens; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000001:Calcimycin; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D013755:Tetradecanoylphorbol Acetate