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

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.

journal_name

Cell

journal_title

Cell

authors

Aguilar OA,Berry R,Rahim MMA,Reichel JJ,Popović B,Tanaka M,Fu Z,Balaji GR,Lau TNH,Tu MM,Kirkham CL,Mahmoud AB,Mesci A,Krmpotić A,Allan DSJ,Makrigiannis AP,Jonjić S,Rossjohn J,Carlyle JR

doi

10.1016/j.cell.2017.03.002

subject

Has Abstract

pub_date

2017-03-23 00:00:00

pages

58-71.e14

issue

1

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(17)30250-7

journal_volume

169

pub_type

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