Study On The Lysising Of Allo-reactional Donor NK Cells On The Recipient Leukemia Cells

Killer cell immunoglobulin-like receptors (KIRs) are members of the immunoglobulin superfamily expressed on the surface of human NK cells and some T-cell subsets. Upon engagement with HLA class I molecules of target cells, KIRs regulate NK cell function by transmitting inhibitory or activating signals. The KIR gene located on Leukocyte receptor complex(LRC) of chromosome 19pl3.4. KIR can be divided into 2(KIR2D) or 3(KRI3D) immunoglobulinlike domains and subdivided into those with long cytoplasmic tails (KIR2DL and KIR3DL) and short cytoplasmic tails (KIR2DS and KIR3DS). The long tail KIRs generate an inhibitory signal through the presence of immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytoplasmic domain. The short tail KIRs owe an activating signal to their association with adaptor proteins bearing immunoreceptor tyrosine-based activating motifs (ITIMs). The KIRs specific recognize HLA class I molecules: KIR2DL2/KIR2DL3 recognizes an epitope shared by group 1 HLA-C allotypes that each have Ser77 (Cwl, Cw3, Cw7, Cw8), KIR2DL1 recognizes an epitope shared by group 2 HLA-C allotypes that each have Asn80(Cw2, Cw4, Cw5, Cw6), KIR3DL1 recognizes an epitope shared by HLA-Bw4 alleles. whereas KIR3DL2 recognizes HLA-A3 and -A11.There is the polymorphism of inhibitory KIR genes in different individuals. During development each NK cell precursor makes a random choice of which KIR gene it will espress, and the different combinations of HLA class I molecules select NK cells that express receptors for self HLA class I . Consequently, the NK cells from any given individual will be alloreactive toward cells from others which lack their KIR ligands and, conversely will be tolerant of cells from anorher individual who has the same or additional KIR ligands.Lots of clinical datas and animal experiments had confirmed that alloreactivity of NK cells because of KIRs epitope mismatch could facilitate engraftment, prevent...