A Viral Immunoevasin Controls Innate Immunity by Targeting the Prototypical Natural Killer Cell Receptor Family

作者：Aguilar Oscar A; Berry Richard; Rahim Mir Munir A; Reichel Johanna J; Popovic Branka; Tanaka Miho; Fu Zhihui; Balaji Gautham R; Lau Timothy N H; Tu Megan M; Kirkham Christina L; Mahmoud Ahmad Bakur; Mesci Aruz; Krmpotic Astrid; Allan David S J; Makrigiannis Andrew P^*; Jonjic Stipan^*; Rossjohn Jamie^*; Carlyle James R^*

来源：Cell, 2017, 169(1): 58-+.

DOI：10.1016/j.cell.2017.03.002

Natural killer (NK) cells play a key role in innate immunity by detecting alterations in self and non-self ligands via paired NK cell receptors (NKRs). Despite identification of numerous NKR-ligand interactions, physiological ligands for the prototypical NK1.1 orphan receptor remain elusive. Here, we identify a viral ligand for the inhibitory and activating NKRP1 (NK1.1) receptors. This murine cytomegalovirus (MCMV)-encoded protein, m12, restrains NK cell effector function by directly engaging the inhibitory NKR-P1B receptor. However, m12 also interacts with the activating NKR-P1A/ C receptors to counterbalance m12 decoy function. Structural analyses reveal that m12 sequesters a large NKR-P1 surface area via a `` polar claw'' mechanism. Polymorphisms in, and ablation of, the viral m12 protein and host NKR-P1B/ C alleles impact NK cell responses in vivo. Thus, we identify the long-sought foreign ligand for this key immunoregulatory NKR family and reveal how it controls the evolutionary balance of immune recognition during host-pathogen interplay.

• 出版日期2017-3-23
• 单位NIH