Effects of methylated CpG islands in promoter region on the expression of KIR3DL1 protein

Abstract

Objective To investigate the effects of methylated CpG islands in the promoter region on the expression of killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1). Methods Three voluntary unpaid blood donors carrying high expression allele KIR3DL1*01502 and three donors carrying low expression allele KIR3DL1*005 were recruited in this study. The nucleotide sequences and the methylated CpG islands in the promoter regions of KIR3DL1*01502 allele and KIR3DL1*005 allele were analyzed. The NK cells expressing KIR3DL1*01502 and KIR3DL1*005 were respectively treated with 5-aza for the demethylation of CpG islands within the promoters. The expression of KIR3DL1 protein on the surface of NK cells was measured with flow cytometer. Results Two differences at nucleotide sites -65 and -269 were detected within the promoter regions of KIR3DL1*01502 and KIR3DL1*005, resulting in two distinct CpG islands. The CpG islands within the promoter of KIR3DL1*01502 allele were highly methylated. The expression of KIR3DL1 protein on NK cells which carried KIR3DL1*01502 allele was significantly increased after the demethylation of CpG islands. However, the treatment of demethylation had no significant effects on the expression KIR3DL1 protein on NK cells harboring KIR3DL1*005 allele. Conclusion The methylated CpG islands within the promoter of KIR3DL1*01502 allele affected the antigen expression on the surface of NK cells. Different KIR3DL1 alleles might show different mechanisms in regulating antigen expression. Key words: Killer cell immunoglobulin like receptor; Methylation; Promoter