The Lautenberg Center for General and Tumor Immunology, The Institute for Medical Research Israel Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
J Immunol. 2010 Mar 15;184(6):2761-8. doi: 10.4049/jimmunol.0901572. Epub 2010 Feb 17.
The killing activity of NK cells is carried out by several activating NK receptors, which includes NKp46, NKp44, NKp30, NKp80, NKG2D, and 2B4. The ligands of these receptors are either self-derived, pathogen-derived, stress-induced ligands or tumor ligands. Importantly, none of these killer ligands are expressed on NK cells and thus self-killing of NK cells is prevented. A notable exception with this regard, is the ligand of the 2B4 receptor. This unusual receptor can exert both activating and inhibiting signals; however, in human NK cells, it serves mainly as an activating receptor. The ligand of 2B4 is CD48 and in contrast to the ligands of all the other NK activating receptors, CD48 is also present on NK cells. Thus, NK cells might be at risk for self-killing that is mediated via the 2B4-CD48 interaction. In this study, we identify a novel mechanism that prevents this self-killing as we show that the association of the MHC class I proteins with the 2B4 receptor, both present on NK cells, results in the attenuation of the 2B4-mediated self-killing of NK cells.
NK 细胞的杀伤活性是通过几种激活 NK 受体来实现的，包括 NKp46、NKp44、NKp30、NKp80、NKG2D 和 2B4。这些受体的配体要么是自身衍生的，要么是病原体衍生的、应激诱导的配体，要么是肿瘤配体。重要的是，这些杀伤配体都不在 NK 细胞上表达，因此可以防止 NK 细胞的自身杀伤。在这方面有一个值得注意的例外，即 2B4 受体的配体。这个不寻常的受体可以发挥激活和抑制信号；然而，在人类 NK 细胞中，它主要作为一种激活受体。2B4 的配体是 CD48，与所有其他 NK 激活受体的配体不同，CD48 也存在于 NK 细胞上。因此，NK 细胞可能面临通过 2B4-CD48 相互作用介导的自身杀伤的风险。在这项研究中，我们确定了一种防止这种自身杀伤的新机制，因为我们表明 MHC Ⅰ类蛋白与存在于 NK 细胞上的 2B4 受体的结合导致 2B4 介导的 NK 细胞自身杀伤的减弱。
