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

Oscar A. Aguilar, Richard Berry, Mir Munir A Rahim, Johanna J. Reichel, Branka Popović, Miho Tanaka, Zhihui Fu, Gautham R. Balaji, Timothy N H Lau, Megan M. Tu, Christina L. Kirkham, Ahmad Bakur Mahmoud, Aruz Mesci, Astrid Krmpotić, David S J Allan, Andrew P. Makrigiannis, Stipan Jonjić, Jamie Rossjohn, James R. Carlyle

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)58-71
Number of pages14
JournalCell
Volume169
Issue number1
DOIs
Publication statusPublished - 23 Mar 2017

Keywords

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

Cite this

Aguilar, O. A., Berry, R., Rahim, M. M. A., Reichel, J. J., Popović, B., Tanaka, M., ... Carlyle, J. R. (2017). A Viral Immunoevasin Controls Innate Immunity by Targeting the Prototypical Natural Killer Cell Receptor Family. Cell, 169(1), 58-71. https://doi.org/10.1016/j.cell.2017.03.002
Aguilar, Oscar A. ; Berry, Richard ; Rahim, Mir Munir A ; Reichel, Johanna J. ; Popović, Branka ; Tanaka, Miho ; Fu, Zhihui ; Balaji, Gautham R. ; Lau, Timothy N H ; Tu, Megan M. ; Kirkham, Christina L. ; Mahmoud, Ahmad Bakur ; Mesci, Aruz ; Krmpotić, Astrid ; Allan, David S J ; Makrigiannis, Andrew P. ; Jonjić, Stipan ; Rossjohn, Jamie ; Carlyle, James R. / A Viral Immunoevasin Controls Innate Immunity by Targeting the Prototypical Natural Killer Cell Receptor Family. In: Cell. 2017 ; Vol. 169, No. 1. pp. 58-71.
@article{eaa02a7e59284d2c8bf063c49371453a,
title = "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.",
keywords = "host-pathogen interactions, murine cytomegalovirus, Natural killer cell, NK1.1 ligand, viral immune evasion",
author = "Aguilar, {Oscar A.} and Richard Berry and Rahim, {Mir Munir A} and Reichel, {Johanna J.} and Branka Popović and Miho Tanaka and Zhihui Fu and Balaji, {Gautham R.} and Lau, {Timothy N H} and Tu, {Megan M.} and Kirkham, {Christina L.} and Mahmoud, {Ahmad Bakur} and Aruz Mesci and Astrid Krmpotić and Allan, {David S J} and Makrigiannis, {Andrew P.} and Stipan Jonjić and Jamie Rossjohn and Carlyle, {James R.}",
year = "2017",
month = "3",
day = "23",
doi = "10.1016/j.cell.2017.03.002",
language = "English",
volume = "169",
pages = "58--71",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier",
number = "1",

}

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 2017, 'A Viral Immunoevasin Controls Innate Immunity by Targeting the Prototypical Natural Killer Cell Receptor Family', Cell, vol. 169, no. 1, pp. 58-71. https://doi.org/10.1016/j.cell.2017.03.002

A Viral Immunoevasin Controls Innate Immunity by Targeting the Prototypical Natural Killer Cell Receptor Family. / Aguilar, Oscar A.; Berry, Richard; Rahim, Mir Munir A; Reichel, Johanna J.; Popović, Branka; Tanaka, Miho; Fu, Zhihui; Balaji, Gautham R.; Lau, Timothy N H; Tu, Megan M.; Kirkham, Christina L.; Mahmoud, Ahmad Bakur; Mesci, Aruz; Krmpotić, Astrid; Allan, David S J; Makrigiannis, Andrew P.; Jonjić, Stipan; Rossjohn, Jamie; Carlyle, James R.

In: Cell, Vol. 169, No. 1, 23.03.2017, p. 58-71.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A Viral Immunoevasin Controls Innate Immunity by Targeting the Prototypical Natural Killer Cell Receptor Family

AU - Aguilar, Oscar A.

AU - Berry, Richard

AU - Rahim, Mir Munir A

AU - Reichel, Johanna J.

AU - Popović, Branka

AU - Tanaka, Miho

AU - Fu, Zhihui

AU - Balaji, Gautham R.

AU - Lau, Timothy N H

AU - Tu, Megan M.

AU - Kirkham, Christina L.

AU - Mahmoud, Ahmad Bakur

AU - Mesci, Aruz

AU - Krmpotić, Astrid

AU - Allan, David S J

AU - Makrigiannis, Andrew P.

AU - Jonjić, Stipan

AU - Rossjohn, Jamie

AU - Carlyle, James R.

PY - 2017/3/23

Y1 - 2017/3/23

N2 - 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.

AB - 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.

KW - host-pathogen interactions

KW - murine cytomegalovirus

KW - Natural killer cell

KW - NK1.1 ligand

KW - viral immune evasion

UR - http://www.scopus.com/inward/record.url?scp=85016146660&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2017.03.002

DO - 10.1016/j.cell.2017.03.002

M3 - Article

VL - 169

SP - 58

EP - 71

JO - Cell

JF - Cell

SN - 0092-8674

IS - 1

ER -