Viral infection modulates Qa-1b in infected and bystander cells to properly direct NK cell killing

J Exp Med. 2021 May 3;218(5):e20201782. doi: 10.1084/jem.20201782.

Abstract

Natural killer (NK) cell activation depends on the signaling balance of activating and inhibitory receptors. CD94 forms inhibitory receptors with NKG2A and activating receptors with NKG2E or NKG2C. We previously demonstrated that CD94-NKG2 on NK cells and its ligand Qa-1b are important for the resistance of C57BL/6 mice to lethal ectromelia virus (ECTV) infection. We now show that NKG2C or NKG2E deficiency does not increase susceptibility to lethal ECTV infection, but overexpression of Qa-1b in infected cells does. We also demonstrate that Qa-1b is down-regulated in infected and up-regulated in bystander inflammatory monocytes and B cells. Moreover, NK cells activated by ECTV infection kill Qa-1b-deficient cells in vitro and in vivo. Thus, during viral infection, recognition of Qa-1b by activating CD94/NKG2 receptors is not critical. Instead, the levels of Qa-1b expression are down-regulated in infected cells but increased in some bystander immune cells to respectively promote or inhibit their killing by activated NK cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / virology
  • Bystander Effect / immunology
  • Cytotoxicity, Immunologic / genetics
  • Cytotoxicity, Immunologic / immunology*
  • Ectromelia virus / immunology*
  • Ectromelia virus / physiology
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / virology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NK Cell Lectin-Like Receptor Subfamily C / genetics
  • NK Cell Lectin-Like Receptor Subfamily C / immunology
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism
  • NK Cell Lectin-Like Receptor Subfamily D / genetics
  • NK Cell Lectin-Like Receptor Subfamily D / immunology
  • NK Cell Lectin-Like Receptor Subfamily D / metabolism
  • Virus Diseases / immunology*
  • Virus Diseases / virology

Substances

  • Histocompatibility Antigens Class I
  • Klrc2 protein, mouse
  • Klrc3 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Q surface antigens