KIR2DL1-HLA signaling pathway: notable inhibition in the cytotoxicity of allo-NK cell against KG1A cell.

Background: KIR2DL1 is an important member of killer cell immunoglobulin-like receptors (KIRs). It recognizes the C2 group of alleles exclusively and delivers signals that inhibit NK cell cytotoxicity. Methods: In this study, NK cells were isolated by magnetic activated cell sorting (MACS) from peripheral blood of 12 healthy unrelated male donors. Flow cytometry (FCM) was used to evaluate the purity of NK cells and phenotypic KIR2DL1 expression on them. The lysis of KG1A and K562 cells by NK cells was analyzed in the lactate dehydrogenase (LDH) assay to investigate whether KIR2DL1 expression on NK cells would affect the cytotoxicity. Results: Significant differences in KIR2DL1 frequency were noted among the donors (range, 27.14% similar to 92.49%). NK cells with lower KIR2DL1 expression exerted higher cytolytic activity against KG1A cells, whereas those with higher KIR2DL1 expression exerted significantly lower lysis against KG1A cells (R-2 = 0.8169, p < 0.05). Conclusions: KIR2DL1 expression frequency was negatively correlated with the cytotoxicity of NK cells against KG1A cells. This study discovered that differential KIR2DL1 expression could positively affect the lytic activity of NK cells against KG1A cells, suggesting potential clinical value of KIR2DL1 selection in the treatment of acute myeloid leukemia (AML) patients.