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

Huei Wei Chan, Zoya B. Kurago, C. Andrew Stewart, Michael J. Wilson, Maureen P. Martin, Brian E. Mace, Mary Carrington, John Trowsdale, Charles T. Lutz

Research output: Contribution to journalArticlepeer-review

163 Scopus citations

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 of 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.

Original languageEnglish (US)
Pages (from-to)245-255
Number of pages11
JournalJournal of Experimental Medicine
Volume197
Issue number2
DOIs
StatePublished - Jan 20 2003

Keywords

  • Alleles
  • DNA methylation
  • Gene expression regulation
  • Killer cells, natural
  • Killer inhibitory receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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