Distinct MHC class I-dependent NK cell-activating receptors control cytomegalovirus infection in different mouse strains

J Exp Med. 2011 May 9;208(5):1105-17. doi: 10.1084/jem.20101831. Epub 2011 Apr 25.

Abstract

Recognition of mouse cytomegalovirus (MCMV)-infected cells by activating NK cell receptors was first described in the context of Ly49H, which confers resistance to C57BL/6 mice. We investigated the ability of other activating Ly49 receptors to recognize MCMV-infected cells in mice from various H-2 backgrounds. We observed that Ly49P1 from NOD/Ltj mice, Ly49L from BALB mice, and Ly49D2 from PWK/Pas mice respond to MCMV-infected cells in the context of H-2D(k) and the viral protein m04/gp34. Recognition was also seen in the H-2(d) and/or H-2(f) contexts, depending on the Ly49 receptor examined, but never in H-2(b). Furthermore, BALB.K (H-2(k)) mice showed reduced viral loads compared with their H-2(d) or H-2(b) congenic partners, a reduction which was dependent on interferon γ secretion by Ly49L(+) NK cells early after infection. Adoptive transfer of Ly49L(+), but not Ly49L(-), NK cells significantly increased resistance against MCMV infection in neonate BALB.K mice. These results suggest that multiple activating Ly49 receptors participate in H-2-dependent recognition of MCMV infection, providing a common mechanism of NK cell-mediated resistance against viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Herpesviridae Infections / genetics
  • Herpesviridae Infections / immunology*
  • Herpesviridae Infections / metabolism
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Immunity, Innate*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Muromegalovirus / genetics
  • Muromegalovirus / immunology*
  • Muromegalovirus / metabolism
  • NK Cell Lectin-Like Receptor Subfamily A / genetics
  • NK Cell Lectin-Like Receptor Subfamily A / immunology*
  • NK Cell Lectin-Like Receptor Subfamily A / metabolism
  • Species Specificity
  • Viral Load / immunology

Substances

  • Histocompatibility Antigens Class I
  • Klra8 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily A