Abstract
Increasingly, roles are emerging for C-type lectin receptors in immune regulation. One receptor whose function has remained largely enigmatic is human NKR-P1A (CD161), present on NK cells and subsets of T cells. In this study, we demonstrate that the lectin-like transcript-1 (LLT1) is a physiologic ligand for NKR-P1A. LLT1-containing liposomes bind to NKR-P1A+ cells, and binding is inhibited by anti-NKR-P1A mAb. Additionally, LLT1 activates NFAT-GFP reporter cells expressing a CD3zeta-NKR-P1A chimeric receptor; reciprocally, reporter cells with a CD3zeta-LLT1 chimeric receptor are stimulated by NKR-P1A. Moreover, LLT1 on target cells can inhibit NK cytotoxicity via interactions with NKR-P1A.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Surface / immunology
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Antigens, Surface / metabolism*
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CD3 Complex / genetics
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Cells, Cultured
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Cytotoxicity, Immunologic
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Green Fluorescent Proteins / genetics
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Humans
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Killer Cells, Natural / immunology
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Lectins, C-Type / immunology
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Lectins, C-Type / metabolism*
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Ligands
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Liposomes
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Lymphocyte Activation
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Mice
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NFATC Transcription Factors / genetics
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NK Cell Lectin-Like Receptor Subfamily B
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Protein Binding
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / metabolism*
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Recombinant Fusion Proteins / genetics
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T-Lymphocyte Subsets / metabolism
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Transfection
Substances
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Antigens, Surface
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CD3 Complex
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CD3 antigen, zeta chain
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CLEC2D protein, human
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KLRB1 protein, human
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Lectins, C-Type
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Ligands
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Liposomes
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NFATC Transcription Factors
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NK Cell Lectin-Like Receptor Subfamily B
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Receptors, Cell Surface
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Recombinant Fusion Proteins
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Green Fluorescent Proteins