Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells

Nat Immunol. 2018 May;19(5):453-463. doi: 10.1038/s41590-018-0082-6. Epub 2018 Apr 9.


Natural killer (NK) cells are innate lymphocytes that lack antigen-specific rearranged receptors, a hallmark of adaptive lymphocytes. In some people infected with human cytomegalovirus (HCMV), an NK cell subset expressing the activating receptor NKG2C undergoes clonal-like expansion that partially resembles anti-viral adaptive responses. However, the viral ligand that drives the activation and differentiation of adaptive NKG2C+ NK cells has remained unclear. Here we found that adaptive NKG2C+ NK cells differentially recognized distinct HCMV strains encoding variable UL40 peptides that, in combination with pro-inflammatory signals, controlled the population expansion and differentiation of adaptive NKG2C+ NK cells. Thus, we propose that polymorphic HCMV peptides contribute to shaping of the heterogeneity of adaptive NKG2C+ NK cell populations among HCMV-seropositive people.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / immunology*
  • Humans
  • Killer Cells, Natural / immunology*
  • NK Cell Lectin-Like Receptor Subfamily C / immunology*
  • Viral Proteins / genetics
  • Viral Proteins / immunology*


  • KLRC2 protein, human
  • NK Cell Lectin-Like Receptor Subfamily C
  • UL40 glycoprotein, Cytomegalovirus
  • Viral Proteins