Abstract
Families of clonally expressed major histocompatibility complex (MHC) class I-specific receptors provide specificity to and regulate the function of natural killer (NK) cells. One of these receptors, mouse Ly49A, is expressed by 20% of NK cells and inhibits the killing of H-2D(d) but not D(b)-expressing target cells. Here, we show that the trans-acting factor TCF-1 binds to two sites in the Ly49A promoter and regulates its activity. Moreover, we find that TCF-1 determines the size of the Ly49A NK cell subset in vivo in a dosage-dependent manner. We propose that clonal Ly49A acquisition during NK cell development is regulated by TCF-1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Ly*
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Binding Sites
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Burkitt Lymphoma / pathology
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Cell Line
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Cell Lineage
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Clone Cells / immunology*
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Cytotoxicity, Immunologic*
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Dose-Response Relationship, Immunologic
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Gene Expression Regulation*
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Green Fluorescent Proteins
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H-2 Antigens / immunology*
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Hepatocyte Nuclear Factor 1-alpha
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Histocompatibility Antigen H-2D
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Humans
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Jurkat Cells
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Lectins, C-Type
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Lymphocyte Count
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Lymphocyte Subsets
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Lymphoid Enhancer-Binding Factor 1
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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NK Cell Lectin-Like Receptor Subfamily A
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Promoter Regions, Genetic
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Radiation Chimera
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Receptors, Immunologic / biosynthesis
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Receptors, Immunologic / genetics*
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Receptors, NK Cell Lectin-Like
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Recombinant Fusion Proteins / metabolism
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Regulatory Sequences, Nucleic Acid
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Self Tolerance*
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T Cell Transcription Factor 1
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Thymoma / pathology
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Thymus Neoplasms / pathology
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transcription, Genetic
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Transfection
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Tumor Cells, Cultured
Substances
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Antigens, Ly
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DNA-Binding Proteins
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H-2 Antigens
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Hepatocyte Nuclear Factor 1-alpha
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Histocompatibility Antigen H-2D
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Hnf1a protein, mouse
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Klra1 protein, mouse
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Lectins, C-Type
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Luminescent Proteins
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Lymphoid Enhancer-Binding Factor 1
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NK Cell Lectin-Like Receptor Subfamily A
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Receptors, Immunologic
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Receptors, NK Cell Lectin-Like
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Recombinant Fusion Proteins
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T Cell Transcription Factor 1
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TCF7 protein, human
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Transcription Factors
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Green Fluorescent Proteins