Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia
Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia
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DOI：
10.1182/blood-2003-01-0019
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发表时间：
2003-08-15
期刊：
影响因子：
20.3
通讯作者：
Steinle, A
中科院分区：
文献类型：
--
作者：
Salih, HR;Antropius, H;Steinle, A
NKG2D配体（NKG2DLs）标记恶性细胞，通过活化免疫受体NKG2D被自然杀伤（NK）细胞和细胞毒性T淋巴细胞识别。这导致了NKG2DL在肿瘤免疫监视中发挥关键作用的假设。人NKG2DLS云母和MICB在体内上皮来源的肿瘤上表达。对于最近描述的另一组人NKG2DL，UL16结合蛋白（ULBP），体内表达尚未确定。在这项研究中，我们使用一组新生成的NKG2DL特异性单克隆抗体研究了NKG2DL在白血病中的表达和功能。我们报告说，白血病患者的细胞表达不同的MIC和ULBP分子的细胞表面与云母最常见的检测。表达云母的患者白血病细胞以NKG2D依赖性方式被INK细胞裂解。患者血清中可溶性云母（sMICA）水平升高，但健康供体血清中无此现象。我们还检测到增加的sMICB水平在患者血清中使用新建立的MICB特异性酶联免疫吸附试验。通过脱落减少白血病MIC表面表达可能会损害INKG2D介导的白血病免疫监视。此外，sMICA和sMICB水平的测定可作为造血系统恶性肿瘤患者的预后参数。(C)2003年，美国血液学会。
NKG2D ligands (NKG2DLs) mark malignant cells for recognition by natural killer (NK) cells and cytotoxic T lymphocytes via the activating immunoreceptor NKG2D. This led to the hypothesis that NKG2DLs play a critical role in tumor immune surveillance. The human NKG2DLS MICA and MICB are expressed on tumors of epithelial origin in vivo. For the other recently described set of human NKG2DLs, the UL16-binding proteins (ULBPs), expression in vivo is as yet undefined. In this study we investigated expression and function of NKG2DLs in leukemia using a panel of newly generated NKG2DL-specific monoclonal antibodies. We report that leukemia cells from patients variously express MIC and ULBP molecules on the cell surface with MICA most frequently detected. Patient leukemia cells expressing MICA were lysed by INK cells in an NKG2D-dependent fashion. Sera of patients, but not of healthy donors, contained elevated levels of soluble MICA (sMICA). We also detected increased sMICB levels in patient sera using a newly established MICB-specific enzyme-linked immunosorbent assay. Reduction of leukemia MIC surface expression by shedding may impair INKG2D-mediated immune surveillance of leukemias. In addition, determination of sMICA and sMICB levels may be implemented as a prognostic parameter in patients with hematopoietic malignancies. (C) 2003 by The American Society of Hematology.