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

doi:10.1016/j.cell.2017.03.002

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 journal › Article › Research › peer-review

66 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 language	English
Pages (from-to)	58-71
Number of pages	14
Journal	Cell
Volume	169
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2017.03.002
Publication status	Published - 23 Mar 2017

Keywords

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

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10.1016/j.cell.2017.03.002

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Aguilar, O. A., Berry, R., Rahim, M. M. A., Reichel, J. J., Popović, B., Tanaka, M., Fu, Z., Balaji, G. R., Lau, T. N. H., Tu, M. M., Kirkham, C. L., Mahmoud, A. B., Mesci, A., Krmpotić, A., Allan, D. S. J., Makrigiannis, A. P., Jonjić, S., Rossjohn, J., & 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

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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 Popovi{\'c} 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 Krmpoti{\'c} and Allan, {David S J} and Makrigiannis, {Andrew P.} and Stipan Jonji{\'c} and Jamie Rossjohn and Carlyle, {James R.}",

year = "2017",

month = mar,

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doi = "10.1016/j.cell.2017.03.002",

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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

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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

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U2 - 10.1016/j.cell.2017.03.002

DO - 10.1016/j.cell.2017.03.002

M3 - Article

AN - SCOPUS:85016146660

SN - 0092-8674

VL - 169

SP - 58

EP - 71

JO - Cell

JF - Cell

IS - 1

ER -

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

Abstract

Keywords

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ARC Centre of Excellence in Advanced Molecular Imaging

Australian Synchrotron

Macromolecular Crystallisation Facility

Cite this

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

Abstract

Keywords

Access to Document

Other files and links

Projects

ARC Centre of Excellence in Advanced Molecular Imaging

Equipment

Australian Synchrotron

Macromolecular Crystallisation Facility

Cite this