The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute, Hadassah Medical School, The Hebrew University, Jerusalem, Israel.
Eur J Immunol. 2013 Aug;43(8):2151-61. doi: 10.1002/eji.201343433. Epub 2013 Jun 21.
The activity of NK cells is controlled by inhibitory and activating receptors. The inhibitory receptors interact mostly with MHC class I proteins, however, inhibitory receptors such as CD300a, which bind to non-MHC class I ligands, also exist. Recently, it was discovered that phosphatidylserine (PS) is a ligand for CD300a and that the interaction between PS expressed on apoptotic cells and CD300a inhibits the uptake of apoptotic cells by phagocytic cells. Whether PS can inhibit NK-cell activity through CD300a is unknown. Here, we have generated specific antibodies directed against CD300a and we used these mAbs to demonstrate that various NK-cell clones express different levels of CD300a. We further demonstrated that both CD300a and its highly homologous molecule CD300c bind to the tumor cells equally well and that they recognize PS and additional unknown ligand(s) expressed by tumor cells. Finally, we showed that blocking the PS-CD300a interaction resulted in increased NK-cell killing of tumor cells. Collectively, we demonstrate a new tumor immune evasion mechanism that is mediated through the interaction between PS and CD300a and we suggest that CD300c, similarly to CD300a, also interacts with PS.
自然杀伤 (NK) 细胞的活性受抑制性和激活性受体的调控。抑制性受体主要与 MHC Ⅰ类蛋白相互作用，但也存在与非 MHC Ⅰ类配体结合的抑制性受体，如 CD300a。最近发现，磷脂酰丝氨酸 (PS) 是 CD300a 的配体，凋亡细胞表面表达的 PS 与 CD300a 的相互作用抑制了吞噬细胞对凋亡细胞的吞噬。PS 是否通过 CD300a 抑制 NK 细胞的活性尚不清楚。本研究生成了针对 CD300a 的特异性抗体，并利用这些 mAb 证实了各种 NK 细胞克隆表达不同水平的 CD300a。我们进一步证实 CD300a 和其高度同源分子 CD300c 同样能与肿瘤细胞结合，且它们能识别 PS 和肿瘤细胞表达的其他未知配体。最后，我们表明阻断 PS-CD300a 相互作用可增强 NK 细胞对肿瘤细胞的杀伤。综上，我们揭示了一种新的肿瘤免疫逃逸机制，该机制通过 PS 与 CD300a 的相互作用介导，且提示 CD300c 与 CD300a 类似，也与 PS 相互作用。
