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KIR Gene and Its Match with HLA-Cw Impact on NK Cell Cytotoxicity

Author: LaiYanLi
Tutor: CaoXiangShan
School: Suzhou University
Course: Blood of
Keywords: Immunoglobulin-like inhibitory receptors CD158 HLA-Cw KIR2DS1 Hematopoietic stem cell transplantation
CLC: R392
Type: Master's thesis
Year: 2009
Downloads: 39
Quote: 0
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Abstract


Objective: To explore the natural killer (natural killer, NK) cell immunoglobulin-like receptor (killerimmunoglobulin-like receptor, KIR) genes and HLA-Cw ligand matching number of NK cell activity; study NK cells KIR2DS1 gene expression of AML (acute myeloid leukemia) effect of target cell killing activity of NK cell KIR / HLA-Cw mismatch (human normal renal function antigen-Cw Cw locus for human leukocyte antigen) anti mechanisms. Methods: Using polymerase chain reaction and sequence-specific primers (PCR-SSP) genotyping technology were detected to 27 healthy donors and 30 patients with HLA-Cw KIR gene; NK cell magnetic bead separation kit negative NK cells as effector cells sorting donor source of high purity; separation of AML patients fresh bone marrow mononuclear cells as target cells; anti-CD158a, CD158b monoclonal antibody blocking NK cell KIR2DL1, KIR2DL2 / 3 receptor; MTT colorimetric assay. KIR receptor blocking KIR genes with different combinations of HLA-Cw NK cells against AML cells before and after destruction rate. Results: bead negative selection of NK cells by flow cytometry, measured sorting CD3-/CD56 16 cell content (90.8 ± 6.08)%; few of NK cell KIR genes and target cells HLA-Cw match NK cell function, 0 matching killing rate (50.66 ± 8.40)%, matching with killing two matching rate (38.28% ± 6.71)%, (19.84 ± 4.32)%, F = 20.226, P <0.001; consistency of KIR / HLA-Cw pairs,> 50% of NK cells expressing inhibitory KIRs killing rate was 10%, the destruction rate of 25% -50% 20% <25% destruction rate 55%, F = 16.276, p <0.001; NK cell inhibitory KIR receptor blocking NK cell killing of target cells enhanced t = -3.00, P = 0.005; C1 group KIR2DS1 NK cell C2 target cells group C1 and C1/C2 group of target cell killing effect than destruction rates were (57.370 ± 1.400)%, (44.190 ± 4.666)%, (36.770 ± 6.56)%, F = 11.87, P = 0.021, KIR receptor blocking more obvious differences, F = 18.72, P = 0.009. Conclusion: NK cell killing mechanisms of AML leukemia cells follow KIR / HLA-Cw ligand-mismatched doctrine; KIR / HLA-Cw the number of matches, KIRs expression levels of NK activity, few match the activity of NK cells anti AML leukemia target cells ability: activating gene KIR2DS1 NK cells on target cells higher than the KIR2DS1-NK cells; C1 group KIR2DS1 NK cells to the group C2 target cell killing rate of a C1 C1/C2 target cells in vitro.

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