Abstract
Class I MHC expression by target cells inhibits lysis mediated by natural killer (NK) cells, often in an allele-specific fashion. It has been proposed that NK cell inhibitory receptors recognize complexes of class I molecules with specific cellular peptides that define self, displacement of which would render cells NK sensitive. By loading the mostly empty Dd class I molecules of cell lines deficient in peptide transporter molecules with synthetic or natural Dd-bound peptides, we have demonstrated specific dose-dependent inhibition of the Ly49+ subset of activated NK cells by class I-peptide complexes. Inhibition occurred with most if not all Dd-binding peptides, suggesting that Ly49+ NK cells recognize class I-peptide complexes largely independently of peptide composition. The results suggest a primary role of NK cells in the destruction of cells that have down-regulated or extinguished cell surface expression of some or all class I molecules.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 3
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / physiology*
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Amino Acid Sequence
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Animals
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Biological Transport
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Cell Line
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Cytotoxicity, Immunologic / physiology*
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Dose-Response Relationship, Immunologic
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Epitopes / immunology
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H-2 Antigens / genetics
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H-2 Antigens / immunology*
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Histocompatibility Antigen H-2D
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Immunologic Surveillance
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Killer Cells, Lymphokine-Activated / immunology
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Killer Cells, Natural / immunology*
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Lymphocyte Activation*
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Protein Binding
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Receptors, Antigen
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Recombinant Fusion Proteins / metabolism
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Transfection
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Tumor Cells, Cultured
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 3
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ATP-Binding Cassette Transporters
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Epitopes
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H-2 Antigens
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Histocompatibility Antigen H-2D
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Receptors, Antigen
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Recombinant Fusion Proteins
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Tap2 protein, mouse