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DNA methylation maintains allele-specific KTR gene expression in human natural killer cells

  1. Author:
    Chan, H. W.
    Kurago, Z. B.
    Stewart, C. A.
    Wilson, M. J.
    Martin, M. P.
    Mace, B. E.
    Carrington, M.
    Trowsdale, J.
    Lutz, C. T.

  2. Author Address

    Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA Univ Iowa, Dept Oral Pathol Oral Radiol & Oral Med, Iowa City, IA 52242 USA Univ Iowa, Grad Program Immunol, Iowa City, IA 52242 USA Univ Iowa, Grad Program Mol Biol, Iowa City, IA 52242 USA Univ Cambridge, Dept Pathol, Div Immunol, Cambridge CB2 1QP, England NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA Lutz CT Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA
    1. Year: 2003
  2. Journal: Journal of Experimental Medicine
    1. 197
    2. 2
    3. Pages: 245-255
  4. Type of Article: Article
  1. 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.

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