Clonal acquisition of the Ly49A NK cell receptor is dependent on the trans-acting factor TCF-1.
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.
Held
W
W
Ludwig Institute for Cancer Research Lausanne Branch, University of Lausanne, Epalinges, Switzerland. wheld@isrec.unil.ch
Kunz
B
B
Lowin-Kropf
B
B
van de Wetering
M
M
Clevers
H
H
D000818:Animals; D000950:Antigens, Ly; D001665:Binding Sites; D002051:Burkitt Lymphoma / Q000473:pathology; D002460:Cell Line; D019070:Cell Lineage; D002999:Clone Cells / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D006183:H-2 Antigens / Q000276:immunology*; D051538:Hepatocyte Nuclear Factor 1-alpha; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011401:Promoter Regions, Genetic; D011828:Radiation Chimera; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D055630:Receptors, NK Cell Lectin-Like; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D017634:Self Tolerance; D051822:T Cell Transcription Factor 1; D013945:Thymoma / Q000473:pathology; D013953:Thymus Neoplasms / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D000950:Antigens, Ly; D004268:DNA-Binding Proteins; D006183:H-2 Antigens; D051538:Hepatocyte Nuclear Factor 1-alpha; D064532:Histocompatibility Antigen H-2D; C496488:Hnf1a protein, mouse; C527088:Klra1 protein, mouse; D037181:Lectins, C-Type; D008164:Luminescent Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D011993:Recombinant Fusion Proteins; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human; D014157:Transcription Factors; D049452:Green Fluorescent Proteins