Activation of cloned human natural killer cells via Fc gamma RIII.
The Fc gamma RIII (CD16) Ag on human NK cells involved in antibody-dependent cellular cytotoxicity has been demonstrated to be an important activation structure. The present studies were carried out to further characterize the functional role of the CD16 Ag and the mechanisms whereby cytotoxicity is activated by using human NK clones. In phenotypic studies Fc gamma RIII was found to be expressed heterogeneously on various human cloned NK cells. Expression on CD3- and CD3+ clones varied with the donor and mAb used for detection. Functional data demonstrated that cytotoxicity against NK-resistant target cells can be induced in CD3-CD16+ NK clones and CD3+CD16+ clones with NK activity when various CD16 mAb were used. CD16 antibodies but not reactive isotype control antibodies induced cytotoxicity. In contrast to complete CD16 antibodies F(ab')2 fragments were not able to activate the cytotoxic mechanism. Both an antibody against FcR on the target cell (Fc gamma RII) and a CD11a antibody blocked induction of cytotoxicity. These results suggest that three steps are critical for activation of CD16+ cells via Fc gamma RIII: 1) specific binding of CD16 antibodies to Fc gamma RIII on effector cells irrespective of the epitope recognized; 2) cross-linking of effector cell CD16 Ag through binding of the Fc site of CD16 antibodies via corresponding FcR on the target cell membrane; and 3) interaction of CD11a/18 molecules with the target cell membrane.
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Abteillung Immunologie und Transfusionsmedizin, Medizinische Hochschule Hannover, FRG.
Uciechowski
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Tetteroo
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Kurrle
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Deicher
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Schmidt
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000943:Antigens, Differentiation / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D001667:Binding, Competitive; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D007074:Immunoglobulin G / Q000378:metabolism* / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D007939:Leukemia L1210 / Q000276:immunology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D011961:Receptors, Fc / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D017452:Receptors, IgG
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D016169:Lymphocyte Function-Associated Antigen-1; D011961:Receptors, Fc; D017452:Receptors, IgG