| Literature DB >> 28340350 |
Oscar A Aguilar1, Richard Berry2, Mir Munir A Rahim3, Johanna J Reichel4, Branka Popović4, Miho Tanaka1, Zhihui Fu5, Gautham R Balaji2, Timothy N H Lau1, Megan M Tu3, Christina L Kirkham1, Ahmad Bakur Mahmoud6, Aruz Mesci1, Astrid Krmpotić4, David S J Allan1, Andrew P Makrigiannis7, Stipan Jonjić8, Jamie Rossjohn9, James R Carlyle10.
Abstract
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 NKR-P1 (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.Entities:
Keywords: NK1.1 ligand; Natural killer cell; host-pathogen interactions; murine cytomegalovirus; viral immune evasion
Mesh：
Substances：
Year: 2017 PMID： 28340350 DOI： 10.1016/j.cell.2017.03.002
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582