Epistasis between mouse Klra and major histocompatibility complex class I loci is associated with a new mechanism of natural killer cell-mediated innate resistance to cytomegalovirus infection

Nat Genet. 2005 Jun;37(6):593-9. doi: 10.1038/ng1564. Epub 2005 May 15.

Abstract

Experimental infection with mouse cytomegalovirus (MCMV) has been used to elucidate the intricate host-pathogen mechanisms that determine innate resistance to infection. Linkage analyses in F(2) progeny from MCMV-resistant MA/My (H2 (k)) and MCMV-susceptible BALB/c (H2 (d)) and BALB.K (H2 (k)) mouse strains indicated that only the combination of alleles encoded by a gene in the Klra (also called Ly49) cluster on chromosome 6, and one in the major histocompatibility complex (H2) on chromosome 17, is associated with virus resistance. We found that natural killer cell-activating receptor Ly49P specifically recognized MCMV-infected cells, dependent on the presence of the H2 (k) haplotype. This binding was blocked using antibodies to H-2D(k) but not antibodies to H-2K(k). These results are suggestive of a new natural killer cell mechanism implicated in MCMV resistance, which depends on the functional interaction of the Ly49P receptor and the major histocompatibility complex class I molecule H-2D(k) on MCMV-infected cells.

Publication types

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

MeSH terms

  • Animals
  • Epistasis, Genetic*
  • Genetic Linkage
  • H-2 Antigens / genetics*
  • Herpesviridae Infections / immunology*
  • Histocompatibility Antigen H-2D
  • Immunity, Innate
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Muromegalovirus
  • Receptors, Immunologic / immunology*

Substances

  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Ly49P receptor
  • Receptors, Immunologic

Associated data

  • GENBANK/AY971805
  • GENBANK/AY971806
  • GENBANK/AY971807