NK cell receptor/H2-Dk-dependent host resistance to viral infection is quantitatively modulated by H2q inhibitory signals.

Abstract

The cytomegalovirus resistance locus Cmv3 has been linked to an epistatic interaction between two loci: a Natural Killer (NK) cell receptor gene and the major histocompatibility complex class I (MHC-I) locus. To demonstrate the interaction between Cmv3 and H2(k), we generated double congenic mice between MA/My and BALB.K mice and an F(2) cross between FVB/N (H-2(q)) and BALB.K (H2(k)) mice, two strains susceptible to mouse cytomegalovirus (MCMV). Only mice expressing H2(k) in conjunction with Cmv3(MA/My) or Cmv3(FVB) were resistant to MCMV infection. Subsequently, an F(3) cross was carried out between transgenic FVB/H2-D(k) and MHC-I deficient mice in which only the progeny expressing Cmv3(FVB) and a single H2-D(k) class-I molecule completely controlled MCMV viral loads. This phenotype was shown to be NK cell-dependent and associated with subsequent NK cell proliferation. Finally, we demonstrated that a number of H2(q) alleles influence the expression level of H2(q) molecules, but not intrinsic functional properties of NK cells; viral loads, however, were quantitatively proportional to the number of H2(q) alleles. Our results support a model in which H-2(q) molecules convey Ly49-dependent inhibitory signals that interfere with the action of H2-D(k) on NK cell activation against MCMV infection. Thus, the integration of activating and inhibitory signals emanating from various MHC-I/NK cell receptor interactions regulates NK cell-mediated control of viral load.

• Authors: Nassima Fodil-Cornu, J Concepción Loredo-Osti, Silvia M Vidal
• Journal: PLoS genetics (PLoS Genet) Vol. 7 Issue 4 Pg. e1001368 (Apr 2011) ISSN: 1553-7404 [Electronic] United States
• PMID: 21533075 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NK Cell Lectin-Like Receptor Subfamily A
• Receptors, Natural Killer Cell

Topics

• Animals
• Cells, Cultured
• Gene Frequency
• Genes, MHC Class I
• Herpesviridae Infections (immunology, virology)
• Immunity, Innate
• Killer Cells, Natural (immunology)
• Mice
• Mice, Congenic
• Mice, Inbred Strains
• Mice, Transgenic
• Muromegalovirus (immunology, pathogenicity)
• NK Cell Lectin-Like Receptor Subfamily A (immunology)
• Phenotype
• Receptors, Natural Killer Cell (genetics, immunology)
• Transgenes
• Viral Load