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Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation

CA. Fielding, MP. Weekes, LV. Nobre, E. Ruckova, GS. Wilkie, JA. Paulo, C. Chang, NM. Suárez, JA. Davies, R. Antrobus, RJ. Stanton, RJ. Aicheler, H. Nichols, B. Vojtesek, J. Trowsdale, AJ. Davison, SP. Gygi, P. Tomasec, PJ. Lehner, GW. Wilkinson,

. 2017 ; 6 (-) : . [pub] 20170210

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural

Persistent link   https://www.medvik.cz/link/bmc18010811

The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel natural killer (NK) cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify ~1300 cell surface and ~7200 whole cell proteins, we demonstrate that the US12 family selectively targets plasma membrane proteins and plays key roles in regulating NK ligands, adhesion molecules and cytokine receptors. US18 and US20 work in concert to suppress cell surface expression of the critical NKp30 ligand B7-H6 thus inhibiting NK cell activation. The US12 family is therefore identified as a major new hub of immune regulation.

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$a The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel natural killer (NK) cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify ~1300 cell surface and ~7200 whole cell proteins, we demonstrate that the US12 family selectively targets plasma membrane proteins and plays key roles in regulating NK ligands, adhesion molecules and cytokine receptors. US18 and US20 work in concert to suppress cell surface expression of the critical NKp30 ligand B7-H6 thus inhibiting NK cell activation. The US12 family is therefore identified as a major new hub of immune regulation.
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$a Weekes, Michael P $u Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom. Department of Cell Biology, Harvard Medical School, Boston, United States.
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$a Nobre, Luis V $u Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
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$a Ruckova, Eva $u Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
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$a Wilkie, Gavin S $u MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom.
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$a Paulo, Joao A $u Department of Cell Biology, Harvard Medical School, Boston, United States.
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$a Chang, Chiwen $u Immunology Division, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
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$a Suárez, Nicolás M $u MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom.
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$a Davies, James A $u Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
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$a Antrobus, Robin $u Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
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$a Stanton, Richard J $u Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
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$a Aicheler, Rebecca J $u Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
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$a Nichols, Hester $u Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
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$a Vojtesek, Borek $u Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
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$a Trowsdale, John $u Immunology Division, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
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$a Davison, Andrew J $u MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom.
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$a Gygi, Steven P $u Department of Cell Biology, Harvard Medical School, Boston, United States.
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$a Tomasec, Peter $u Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
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$a Lehner, Paul J $u Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
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$a Wilkinson, Gavin W G $u Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
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