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

eLife | 2017

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.

Pubmed ID: 28186488 RIS Download

Research resources used in this publication

Antibodies used in this publication

Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: G9827961
  • Agency: Wellcome Trust, United Kingdom
    Id: WT090323MA
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12014/12
  • Agency: Medical Research Council, United Kingdom
    Id: G0901682
  • Agency: HCRW_, United Kingdom
    Id: HCRW_HS-14-11
  • Agency: NIDDK NIH HHS, United States
    Id: K01 DK098285
  • Agency: Wellcome Trust, United Kingdom
    Id: 100140
  • Agency: Wellcome Trust, United Kingdom
    Id: WT101835
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12014/3
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L018373/1
  • Agency: Medical Research Council, United Kingdom
    Id: G0700142
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L008734/1
  • Agency: Wellcome Trust, United Kingdom
    Id: 108070/Z/15/Z
  • Agency: Medical Research Council, United Kingdom
    Id: G1000236

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