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

Fielding, Ceri A. ORCID:, Weekes, Michael P., Nobre, Luis V., Ruckova, Eva, Wilkie, Gavin S., Paulo, Joao A., Chang, Chiwen, Suárez, Nicolás M., Davies, James A., Antrobus, Robin, Stanton, Richard J. ORCID:, Aicheler, Rebecca J, Nichols, Hester ORCID:, Vojtesek, Borek, Trowsdale, John, Davison, Andrew J., Gygi, Steven P., Tomasec, Peter, Lehner, Paul J. and Wilkinson, Gavin W. G. ORCID: 2017. Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation. eLife 6 , e22206. 10.7554/eLife.22206

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The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel NK cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify ~1,300 cell surface and ~7,200 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QH Natural history > QH426 Genetics
Publisher: eLife Sciences Publications
ISSN: 2050-084X
Funders: MRC
Date of First Compliant Deposit: 13 February 2017
Date of Acceptance: 9 February 2017
Last Modified: 19 Nov 2023 15:54

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