课题组前期发现异基因造血干细胞移植冶疗AML中，供者KIR Bx1型与其他B组基因型作用相反，降低了移植后生存/无病生存，在此基础上结合国外相关研究成果，提出Tel端KIR2DS5编码蛋白氨基酸残基R158G的改变，阻碍了蛋白糖基化修饰从而影响膜受体的表达，导致携带该KIR2DS5等位基因的活化NK细胞对髓系白血病细胞杀伤能力减弱的设想。本研究拟通过基因、分子和细胞不同层面从以下3方面展开研究：1）探讨Cen端/Tel端KIR2DS5编码蛋白在细胞表面和细胞内的表达量与等位基因型的关系；2）阐明Tel端KIR2DS5编码受体在细胞表面低表达的分子机制；3）体外观察携带不同KIR2DS5等位基因对活化NK细胞杀伤髓系白血病细胞的影响。研究结果可望揭示接受Bx1型供者移植的AML患者术后生存/无病生存降低的发病机制、为NK细胞介导的个体化治疗提供新靶点，为扩大潜在供者选择范围提供新的理论依据。

Donor killer immunoglobulin-like receptors (KIR) group B genotypes (Bx) are the most preferable KIR gene motifs for hematopoietic stem cell transplantation (HSCT). However, a risk of decreased OS and RFS in transplants from Bx1 donors was previously observed for AML patients. Since the KIR2DS5 alleles are assigned restrictively to centromeric (Cen) or telomeric (Tel) regions, it is hypothesized that the mutation of Tel-KIR2DS5 at residue 158 may impact the efficiency of glycosylation and appears to be responsible for the lower level of cell surface expression compared to Cen-KIR2DS5; and this variation greatly reduced the cytolytic activity of the NK cells carrying Tel-KIR2DS5 receptors against the myeloid leukemia cells and cytokine release. To test the hypothesis, first of all, we analyze the impact of the allele variation on cell surface /inter-cellular expression. Next, we focus on the potential molecular mechanisms accounting for the lower levels of cell surface expression for KIR2DS5 variants on telomeric region. Lastly, killing experiment and detection of cytokine release are used to identify this variation inhibits the NK cells expressing Tel-KIR2DS5 to produce interferon-γ and kill myeloid leukemia cells in vitro. The present study may reveal the process of the decreased OS/RFS in transplants from Bx1 donors for treatment of AML. Also it may benefit in providing theoretical and practical basis to perform NK-mediated individualized treatment and thus expanding the potential donors.