Interaction of Ly-49D+ NK Cells with H-2Dd Target Cells Leads to Dap-12 Phosphorylation and IFN-γ Secretion
Autor: | Anna T. Mason, Llewellyn H. Mason, John R. Ortaldo, Jamie Willette-Brown, Daniel W. McVicar |
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Rok vydání: | 2000 |
Předmět: |
Cytotoxicity
Immunologic Immunology Biology Transfection Cell Line Interferon-gamma Mice Interleukin 21 Tumor Cells Cultured Animals Antigens Ly Immunology and Allergy Lectins C-Type Secretion Phosphorylation Receptors Immunologic Histocompatibility Antigen H-2D Receptor Adaptor Proteins Signal Transducing Membrane Glycoproteins Janus kinase 3 H-2 Antigens Membrane Proteins Cytotoxicity Tests Immunologic Phosphoproteins Ligand (biochemistry) Molecular biology Rats Killer Cells Natural Mice Inbred C57BL Interleukin 12 Cytokine secretion Receptors NK Cell Lectin-Like |
Zdroj: | The Journal of Immunology. 164:603-611 |
ISSN: | 1550-6606 0022-1767 |
Popis: | Murine Ly-49D augments NK cell function upon recognition of target cells expressing H-2Dd. Ly-49D activation is mediated by the immunoreceptor tyrosine-based activation motif-containing signaling moiety Dap-12. In this report we demonstrate that Ly-49D receptor ligation can lead to the rapid and potent secretion of IFN-γ. Cytokine secretion can be induced from Ly-49D+ NK cells after receptor ligation with Ab or after interaction with target cells expressing their H-2Dd ligand. Consistent with the dominant inhibitory function of Ly-49G, NK cells coexpressing Ly-49D and Ly-49G show a profound reduction in IFN-γ secretion after interaction with targets expressing their common ligand, H-2Dd. Importantly, we are able to demonstrate for the first time that effector/target cell interactions using Ly-49D+ NK cells and H-2Dd targets result in the rapid phosphorylation of Dap-12. However, Dap-12 is not phosphorylated when Ly-49D+ NK cells coexpress the inhibitory receptor, Ly-49G. These studies are novel in describing Ly-49 activation vs inhibition, where two Ly-49 receptors recognize the same class I ligand, with the dominant inhibitory receptor down-regulating phosphorylation of Dap-12, cytokine secretion, and cytotoxicity in NK cells. |
Databáze: | OpenAIRE |
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