Ferez Maria, Knudson Cory J, Lev Avital, Wong Eric B, Alves-Peixoto Pedro, Tang Lingjuan, Stotesbury Colby, Sigal Luis J
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA.
Fox Chase Cancer Center, Philadelphia, PA.
J Exp Med. 2021 May 3;218(5). doi: 10.1084/jem.20201782.
Natural killer (NK) cell activation depends on the signaling balance of activating and inhibitory receptors. CD94 forms inhibitory receptors with NKG2A and activating receptors with NKG2E or NKG2C. We previously demonstrated that CD94-NKG2 on NK cells and its ligand Qa-1b are important for the resistance of C57BL/6 mice to lethal ectromelia virus (ECTV) infection. We now show that NKG2C or NKG2E deficiency does not increase susceptibility to lethal ECTV infection, but overexpression of Qa-1b in infected cells does. We also demonstrate that Qa-1b is down-regulated in infected and up-regulated in bystander inflammatory monocytes and B cells. Moreover, NK cells activated by ECTV infection kill Qa-1b-deficient cells in vitro and in vivo. Thus, during viral infection, recognition of Qa-1b by activating CD94/NKG2 receptors is not critical. Instead, the levels of Qa-1b expression are down-regulated in infected cells but increased in some bystander immune cells to respectively promote or inhibit their killing by activated NK cells.
自然杀伤（NK）细胞的激活取决于激活受体和抑制受体的信号平衡。CD94与NKG2A形成抑制性受体，与NKG2E或NKG2C形成激活性受体。我们之前证明，NK细胞上的CD94-NKG2及其配体Qa-1b对于C57BL/6小鼠抵抗致死性脱脚病病毒（ECTV）感染很重要。我们现在发现，NKG2C或NKG2E缺陷并不会增加对致死性ECTV感染的易感性，但感染细胞中Qa-1b的过表达会增加易感性。我们还证明，Qa-1b在感染细胞中下调，而在旁观炎症单核细胞和B细胞中上调。此外，ECTV感染激活的NK细胞在体外和体内均可杀伤Qa-1b缺陷细胞。因此，在病毒感染期间，激活型CD94/NKG2受体对Qa-1b的识别并不关键。相反，Qa-1b的表达水平在感染细胞中下调，但在一些旁观免疫细胞中升高，分别促进或抑制被激活的NK细胞对它们的杀伤。
