Cutting Edge: NKG2D Signaling Enhances NK Cell Responses but Alone Is Insufficient To Drive Expansion during Mouse Cytomegalovirus Infection

J Immunol. 2017 Sep 1;199(5):1567-1571. doi: 10.4049/jimmunol.1700799. Epub 2017 Jul 31.


NK cells play a critical role in host defense against viruses. In this study, we investigated the role of NKG2D in the expansion of NK cells after mouse CMV (MCMV) infection. Wild-type and NKG2D-deficient (Klrk1-/- ) Ly49H+ NK cells proliferated robustly when infected with MCMV strains engineered to allow expression of NKG2D ligands, which enhanced the response of wild-type NK cells. Naive NK cells exclusively express NKG2D-L, which pairs only with DAP10, whereas NKG2D-S expressed by activated NK cells pairs with DAP10 and DAP12, similar to Ly49H. However, NKG2D alone was unable to drive robust expansion of Ly49H- NK cells when mice were infected with these MCMV strains, likely because NKG2D-S was only transiently expressed postinfection. These findings demonstrate that NKG2D augments Ly49H-dependent proliferation of NK cells; however, NKG2D signaling alone is inadequate for expansion of NK cells, likely due to only transient expression of the NKG2D-DAP12 complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Herpesviridae Infections / immunology*
  • Immunity, Innate
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muromegalovirus / immunology*
  • NK Cell Lectin-Like Receptor Subfamily A / genetics
  • NK Cell Lectin-Like Receptor Subfamily A / metabolism*
  • NK Cell Lectin-Like Receptor Subfamily K / genetics
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism*
  • Protein Binding
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Signal Transduction


  • Adaptor Proteins, Signal Transducing
  • Hcst protein, mouse
  • Klra8 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily A
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Tyrobp protein, mouse