Format

Send to

Choose Destination
Cell. 2017 Mar 23;169(1):58-71.e14. doi: 10.1016/j.cell.2017.03.002.

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

Author information

1
Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada; Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
2
Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia.
3
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
4
Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
5
Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
6
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada; College of Applied Medical Sciences, Taibah University, 30001 Madinah Munawwarah, Kingdom of Saudi Arabia.
7
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada. Electronic address: andrew.makrigiannis@dal.ca.
8
Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. Electronic address: stipan.jonjic@medri.uniri.hr.
9
Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia; Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. Electronic address: jamie.rossjohn@monash.edu.
10
Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada; Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada. Electronic address: james.carlyle@utoronto.ca.

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.

KEYWORDS:

NK1.1 ligand; Natural killer cell; host-pathogen interactions; murine cytomegalovirus; viral immune evasion

PMID:
28340350
DOI:
10.1016/j.cell.2017.03.002
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center