Crucial role of DNA methylation in determination of clonally distributed killer cell Ig-like receptor expression patterns in NK cells.
نویسندگان
چکیده
Human NK cells are characterized by the expression of surface receptors of the killer cell Ig-like receptor (KIR) family, which are involved in the specific recognition of pathogenic target cells. Each NK cell expresses and maintains an individual subset of inhibitory and stimulatory KIR and in this way contributes to a diversified NK cell repertoire. To date, the molecular basis for generation of clonally distributed KIR expression patterns has been elusive. Here, analyses of DNA methylation patterns of KIR genes in NK cell lines as well as in NK cells, freshly isolated from peripheral blood, demonstrated that a small CpG island surrounding the transcriptional start site of each KIR gene is consistently demethylated in expressed KIR and methylated in unexpressed KIR. DNA-demethylating treatment resulted in a rapid and stable induction of transcription and cell surface expression of all formerly unexpressed KIR in NK cell lines, NK cell clones, and freshly isolated NK cells, but not in other cell types. In vitro methylation of KIR CpG islands repressed reporter gene expression in NK cells. We conclude that clonal patterns of KIR expression are mainly epigenetically determined and maintained through DNA methylation.
منابع مشابه
Killer Cell Immunoglobulin-Like Receptors Influence the Innate and Adaptive Immune Responses
Natural killer (NK) cells are a subset of lymphocytes which play a crucial role in early innate immune response against infection and tumor transformation. Furthermore, they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF) prompting adaptive immu-nity. NK cells distinguish the unhealthy cells from the healthy ones through an array of cell-surface receptors. Human NK cells use inhibi...
متن کاملP-164: Human Leukocyte Antigen Class Ib and Pregnancy Success
Background: During pregnancy, the maternal immune system is in close contact with cells and tissue from the semiallogenic fetus .The Human Leucocyte Antigen (HLA) class Ib molecules, HLA-E, -F and -G, are expressed at the materno-fetal interface. Because of the apparent immunoregulatory functions of these proteins, they may be involved in successful acceptance of the semi-allogenic fetus during...
متن کاملP-145: Role of Human Leukocyte Antigen in Miscarriage
Background: During pregnancy, the maternal immune system is in close contact with cells and tissue from the semiallogenic fetus .The human leucocyte antigen (HLA) class Ib molecules, HLA-E, -F and -G, are expressed at the materno-fetal interface. Because of the apparent immunoregulatory functions of these proteins, they may be involved in successful acceptance of the semi-allogenic fetus during...
متن کاملThree structurally and functionally divergent kinds of promoters regulate expression of clonally distributed killer cell Ig-like receptors (KIR), of KIR2DL4, and of KIR3DL3.
The generation of killer cell Ig-like receptor (KIR) expression patterns in NK cells involves variegated silencing of KIR genes by DNA methylation. To identify regulatory elements involved in KIR gene activation, upstream regions of KIR genes were functionally characterized in NK3.3 cells as well as in primary NK cells. Three kinds of KIR promoters were defined, controlling clonally expressed K...
متن کاملEvidence for epigenetic maintenance of Ly49a monoallelic gene expression.
Although structurally unrelated, the human killer cell Ig-like (KIR) genes and the rodent lectin-like Ly49 genes serve similar functional roles in NK cells. Moreover, both gene families display variegated, monoallelic expression patterns established at the transcriptional level. DNA methylation has been shown to play an important role in maintenance of expression patterns of KIR genes, which ha...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of immunology
دوره 169 8 شماره
صفحات -
تاریخ انتشار 2002