title: Abnormal T cells from MRL/Mp-lpr/lpr mice do not respond to anti-T-cell-receptor antibody or tumor promoter and calcium ionophore A23187 despite the presence of the T-cell-receptor complex and protein kinase c.
abstract: Abnormal T cells from autoimmune MRL/Mp-lpr/lpr mice express T-cell-receptor complexes on their surfaces. These receptors are nonfunctional, since monoclonal anti-T-cell-receptor antibody-conjugated beads, which normally activate receptor-bearing T cells, were unable to activate these abnormal T cells. In addition, these abnormal T cells are unresponsive to the synergistic effect of phorbolmyristate acetate (PMA) and calcium ionophore A23187, as quantitated by proliferation, interleukin-2(IL-2) production, and the expression of IL-2 receptors. The failure of abnormal T cells to respond to PMA is not due to the absence of PMA receptors since Scatchard plot analysis reveals that there are 1-1.5 X 10(5) PMA-binding sites/cell with a Kd of 6-10 nM on these abnormal T cells. Similar to normal T lymphocytes, protein kinase c activity can be readily detected in the cytosolic fraction of these abnormal T cells. More importantly, in vitro culture of the abnormal T cells with PMA results in translocation of protein kinase c activity from the cytosolic fraction to the membrane fraction. From these experiments we concluded that the defect in the signal-transducing machinery in MRL/Mp-lpr/lpr T cells is not due to the lack of PMA receptors or the absence of protein kinase c activity, but may result from events which occur after the activation and translocation of protein kinase c. However, whether defects in response to a physiological stimulus (i.e., anti-receptor antibody) could occur in a step prior to protein kinase c activation remains to be determined.
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000954:Antigens, Surface / Q000302:isolation & purification; D029742:Caenorhabditis elegans Proteins; D000001:Calcimycin / Q000494:pharmacology*; D002352:Carrier Proteins; D003600:Cytosol / Q000201:enzymology; D004357:Drug Synergism; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000032:analysis / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011955:Receptors, Drug; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D000001:Calcimycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate