Morris Margaret A, Koulich Elena, Liu Jingxuan, Arora Veera, George Thaddeus C, Schatzle John D, Kumar Vinay, Bennett Michael
Department of Pathology, Laboratory of Molecular Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9072, USA.
Transplantation. 2002 Nov 27;74(10):1449-54. doi: 10.1097/00007890-200211270-00018.
Natural killer (NK) cells use inhibitory Ly49 receptors to differentiate self from foreign cells based on interactions with major histocompatibility (MHC) class I molecules. Inhibitory receptors may recognize multiple MHC class I molecules. Studies to define ligands for the Ly49 receptors are complicated by the fact that receptors are expressed in overlapping subsets on NK cells. Binding studies can predict which MHC class I molecules are ligands for Ly49 receptors, but functional tests are required to substantiate results from binding studies.
We developed Ly49 receptor transgenic mice and studied the function of Ly49I(B6) in FVB.Ly49I(B6) transgenic mice using bone marrow transplantation assays to determine additional functional ligands for Ly49I(B6). We have also used fluorescence-activated cell sorting to isolate specific populations of B6 NK cells bearing Ly49I for use as effectors in chromium-release assays against a panel of Concanavalin A blast targets.
Bone marrow transplantation studies indicate that H2-K(b), H2(s), and H2(v) serve as functional ligands for Ly49I(B6). In vitro cytotoxicity assays indicate that Ly49I recognizes H2(q), but not H2(d) or H2(k), target cells to inhibit NK killing.
These data add support to previous binding studies by showing functional interactions between the B6-strain Ly49I and H2-K(b), H2(s), H2(v), and H2(q) class I antigens.
自然杀伤（NK）细胞利用抑制性Ly49受体，通过与主要组织相容性（MHC）I类分子的相互作用来区分自身与外来细胞。抑制性受体可能识别多种MHC I类分子。由于受体在NK细胞上以重叠的亚群形式表达，因此定义Ly49受体配体的研究变得复杂。结合研究可以预测哪些MHC I类分子是Ly49受体的配体，但需要功能测试来证实结合研究的结果。
我们构建了Ly49受体转基因小鼠，并使用骨髓移植试验研究了FVB.Ly49I（B6）转基因小鼠中Ly49I（B6）的功能，以确定Ly49I（B6）的其他功能性配体。我们还使用荧光激活细胞分选技术分离出携带Ly49I的B6 NK细胞特定群体，用作针对一组伴刀豆球蛋白A刺激靶细胞的铬释放试验中的效应细胞。
骨髓移植研究表明，H2-K(b)、H2(s)和H2(v)作为Ly49I（B6）的功能性配体。体外细胞毒性试验表明，Ly49I识别H2(q)靶细胞，但不识别H2(d)或H2(k)靶细胞，以抑制NK杀伤。
这些数据通过显示B6品系Ly49I与H2-K(b)、H2(s)、H2(v)和H2(q) I类抗原之间的功能相互作用，为先前的结合研究提供了支持。
