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.
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.
Desrosiers
Marie-Pierre
MP
Department of Human Genetics, McGill University, Montreal, Quebec, H3A 1B1, Canada.
Kielczewska
Agnieszka
A
Loredo-Osti
J-C
JC
Adam
Sonia Girard
SG
Makrigiannis
Andrew P
AP
Lemieux
Suzanne
S
Pham
Trung
T
Lodoen
Melissa B
MB
Morgan
Kenneth
K
Lanier
Lewis L
LL
Vidal
Silvia M
SM
D000818:Animals; D004843:Epistasis, Genetic; D008040:Genetic Linkage; D006183:H-2 Antigens / Q000235:genetics*; D006566:Herpesviridae Infections / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D018146:Muromegalovirus; D011971:Receptors, Immunologic / Q000276:immunology*
D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; C400050:Ly49P receptor; D011971:Receptors, Immunologic