title: 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.affiliation: Department of Human Genetics, McGill University, Life Sciences Complex, Montreal, Canada.
authors.forename: Nassima
authors.initials: N
authors.lastname: Fodil-Cornu
authors.forename: J Concepción
authors.initials: JC
authors.lastname: Loredo-Osti
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Vidal
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005787:Gene Frequency; D005805:Genes, MHC Class I; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D020297:Mice, Congenic; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000276:immunology* / Q000472:pathogenicity; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000276:immunology*; D010641:Phenotype; D055607:Receptors, Natural Killer Cell / Q000235:genetics* / Q000276:immunology; D019076:Transgenes; D019562:Viral Load
chemical_list: D055650:NK Cell Lectin-Like Receptor Subfamily A; D055607:Receptors, Natural Killer Cell