Shaping the human NK cell repertoire: an epigenetic glance at KIR gene regulation

Human NK cells are equipped with arrays of inhibitory and stimulatory KIR receptors, many of them specific for HLA class I molecules on target cells. These NK receptors enable the recognition of virally infected as well as malignantly transformed target cells, which have downregulated the expression of single or multiple HLA class I products. KIR are expressed in clonally distributed ways leading to highly individualized but stable NK cell repertoires. Here, progress is reviewed toward understanding the molecular mechanisms that govern the unusual expression characteristics of KIR genes. Recent results suggest that DNA methylation plays a crucial role in shaping the KIR repertoire and underline the importance of epigenetic mechanisms as regulatory switches in the immune system.