Binding of diverse peptides to MHC class I molecules inhibits target cell lysis by activated natural killer cells.
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.
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Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
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D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D007157:Immunologic Surveillance; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011485:Protein Binding; D011946:Receptors, Antigen; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000939:Epitopes; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D011946:Receptors, Antigen; D011993:Recombinant Fusion Proteins; C489516:Tap2 protein, mouse