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

Cell | Mar 23, 2017

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.

Pubmed ID: 28340350 RIS Download

Mesh terms: Animals | Antigens, Ly | Cell Line | HEK293 Cells | Host-Pathogen Interactions | Humans | Immune Evasion | Immunity, Innate | Killer Cells, Natural | Mice | Muromegalovirus | NIH 3T3 Cells | NK Cell Lectin-Like Receptor Subfamily B | Rats | Receptors, Natural Killer Cell | Viral Proteins

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This is a list of tools and resources that we have found mentioned in this publication.


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