George T C, Mason L H, Ortaldo J R, Kumar V, Bennett M
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
J Immunol. 1999 Feb 15;162(4):2035-43.
Members of the murine Ly49 family of receptors have been shown to inhibit and activate NK cell function. Subsets of Ly49-expressing NK cells mediate the rejection of bone marrow cell allografts and the lysis of allogeneic lymphoblasts. In this report we have studied Ly49-mediated positive and negative signaling in an in vitro cytotoxicity assay using sorted NK cell subsets as effectors and a panel of 51Cr-labeled Con A lymphoblasts as targets in the presence or the absence of Abs to Ly49 and/or class I molecules. Our results demonstrate that the activating receptor Ly49D delivers stimulatory signals for target cell lysis upon interacting with H2-Dd, Dr, and Dsp2, but not H2b or H2k class I Ags. On the other hand, the inhibitory receptor Ly49G2 delivers negative signals for target cell lysis upon interacting with Dd, Dr, and H2k, but not H2b or Dsp2, class I Ags. Furthermore, Ly49-mediated negative signaling dominates Ly49D-mediated positive signaling. Thus, lysis of class I MHC-bearing targets by NK cells is not merely the consequence of the absence of an Ly49-mediated negative signal, but also requires positive recognition of class I molecules by certain Ly49 receptors. Activation of NK cells by nonself class I molecules was not predicted by the missing self hypothesis.
小鼠Ly49受体家族的成员已被证明可抑制和激活自然杀伤（NK）细胞功能。表达Ly49的NK细胞亚群介导骨髓细胞同种异体移植的排斥反应以及同种异体淋巴母细胞的裂解。在本报告中，我们使用分选的NK细胞亚群作为效应细胞，并以一组51Cr标记的刀豆蛋白A淋巴母细胞作为靶细胞，在存在或不存在抗Ly49和/或I类分子抗体的情况下，通过体外细胞毒性试验研究了Ly49介导的正向和负向信号传导。我们的结果表明，激活受体Ly49D与H2-Dd、Dr和Dsp2相互作用时，会传递刺激信号以促进靶细胞裂解，但与H2b或H2k I类抗原相互作用时则不会。另一方面，抑制性受体Ly49G2与Dd、Dr和H2k相互作用时，会传递负向信号以抑制靶细胞裂解，但与H2b或Dsp2 I类抗原相互作用时则不会。此外，Ly49介导的负向信号传导在Ly49D介导的正向信号传导中占主导地位。因此，NK细胞对携带I类主要组织相容性复合体（MHC）的靶细胞的裂解不仅是缺乏Ly49介导的负向信号的结果，还需要某些Ly49受体对I类分子的正向识别。非自身I类分子对NK细胞的激活无法用“缺失自我”假说来预测。
