Abstract
Limited information is available on the surface molecules that are involved in natural killer (NK) cell triggering. In this study, we selected the BAB281 monoclonal antibody (mAb) on the basis of its ability to trigger NK-mediated target cell lysis. BAB281 identified a novel NK cell-specific surface molecule of 46 kD (p46) that is expressed by all resting or activated NK cells. Importantly, unlike the NK cell antigens identified so far, the expression of p46 was strictly confined to NK cells. Upon mAb-mediated cross-linking, p46 molecules induced strong cell triggering leading to [Ca2+]i increases, lymphokine production, and cytolytic activity both in resting NK cells and NK cell clones. The p46-mediated induction of Ca2+ increases or triggering of cytolytic activity was downregulated by the simultaneous engagement of inhibitory receptors including p58, p70, and CD94/NKG2A. Both the unique cellular distribution and functional capability of p46 molecules suggest a possible role in the mechanisms of non-major histocompatibility complex-restricted cytolysis mediated by human NK cells.
MeSH terms
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Amidohydrolases / metabolism
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Antibodies, Monoclonal / immunology
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Antigens, CD / immunology
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Antigens, CD / metabolism
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Antigens, Surface / analysis
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Antigens, Surface / immunology*
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Calcium / metabolism
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Clone Cells
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Cross-Linking Reagents / metabolism
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Cytokines / biosynthesis
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Cytotoxicity Tests, Immunologic / methods
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Cytotoxicity, Immunologic / immunology
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Down-Regulation
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Glycosylation
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Hexosaminidases / metabolism
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Humans
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Killer Cells, Natural / immunology*
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Lectins, C-Type*
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Lymphocyte Activation*
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism
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NK Cell Lectin-Like Receptor Subfamily D
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Natural Cytotoxicity Triggering Receptor 1
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Neuraminidase / metabolism
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Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism
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Receptors, KIR
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Receptors, KIR2DL3
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Surface
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Cross-Linking Reagents
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Cytokines
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KIR2DL3 protein, human
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KLRD1 protein, human
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Lectins, C-Type
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Membrane Glycoproteins
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NCR1 protein, human
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NK Cell Lectin-Like Receptor Subfamily D
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Natural Cytotoxicity Triggering Receptor 1
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Receptors, Immunologic
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Receptors, KIR
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Receptors, KIR2DL3
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p70 natural killer cell receptor
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Hexosaminidases
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Neuraminidase
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glycopeptide alpha-N-acetylgalactosaminidase
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Amidohydrolases
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Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
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Calcium