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

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Author
Fielding, C.A.
Weekes, M.P.
Nobre, L.V.
Ruckova, E.
Wilkie, G.S.
Paulo, J.A.
Chang, C.
Suárez, N.M.
Davies, J.A.
Antrobus, R.
Stanton, R.J.
Aicheler, Rebecca
Date
2017-02-10
Acceptance date
2017-03-09
Type
Article
Publisher
eLife
ISSN
2050-084X
Metadata
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Abstract
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.
Journal/conference proceeding
eLife
Citation
Fielding, C.A., Weekes, M.P., Nobre, L.V., Ruckova, E., Wilkie, G.S., Paulo, J.A., Chang, C., Suárez, N.M., Davies, J.A., Antrobus, R., Stanton, R.J., Aicheler, R. et al (2017) 'Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation', Elife, 6: e22206. DOI: 10.7554/eLife.22206
URI
http://hdl.handle.net/10369/9371
DOI
https://doi.org/10.7554/eLife.22206
Description
This article was published open access in eLife on 10 February 2017, available open access at https://doi.org/10.7554/eLife.22206
Rights
https://creativecommons.org/licenses/by/4.0/
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