title: DNA methylation maintains allele-specific KIR gene expression in human natural killer cells.
abstract: Killer immunoglobulin-like receptors (KIR) bind self-major histocompatibility complex class I molecules, allowing natural killer (NK) cells to recognize aberrant cells that have down-regulated class I. NK cells express variable numbers and combinations of highly homologous clonally restricted KIR genes, but uniformly express KIR2DL4. We show that NK clones express both 2DL4 alleles and either one or both alleles of the clonally restricted KIR 3DL1 and 3DL2 genes. Despite allele-independent expression, 3DL1 alleles differed in the core promoter by only one or two nucleotides. Allele-specific 3DL1 gene expression correlated with promoter and 5' gene DNA hypomethylation in NK cells in vitro and in vivo. The DNA methylase inhibitor, 5-aza-2'-deoxycytidine, induced KIR DNA hypomethylation and heterogeneous expression of multiple KIR genes. Thus, NK cells use DNA methylation to maintain clonally restricted expression of highly homologous KIR genes and alleles.
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Huei-Wei
authors.initials: HW
authors.lastname: Chan
authors.forename: Zoya B
authors.initials: ZB
authors.lastname: Kurago
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Stewart
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wilson
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Martin
authors.forename: Brian E
authors.initials: BE
authors.lastname: Mace
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: John
authors.initials: J
authors.lastname: Trowsdale
authors.forename: Charles T
authors.initials: CT
authors.lastname: Lutz
mesh_terms: D000483:Alleles; D002460:Cell Line; D002999:Clone Cells; D019175:DNA Methylation; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics*; D054340:Receptors, KIR; D054345:Receptors, KIR2DL4; D054341:Receptors, KIR3DL1; D054347:Receptors, KIR3DL2
chemical_list: D015395:Histocompatibility Antigens Class I; C515079:KIR2DL4 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054345:Receptors, KIR2DL4; D054341:Receptors, KIR3DL1; D054347:Receptors, KIR3DL2