Suppression of H-2b-associated resistance to Friend erythroleukemia virus by a class I gene from the H-2d major histocompatibility complex haplotype.
Mice homozygous for the H-2d haplotype at the major histocompatibility complex are markedly more susceptible to erythroleukemia induction by the Friend isolate of murine leukemia retrovirus (FV) than are congenic mice homozygous for the H-2b haplotype. The resistance conferred by the H-2b haplotype is recessive in this cross, since heterozygous F1 mice are as susceptible as parental strain H-2d homozygotes. However, H-2b-associated resistance is not an intrinsically recessive trait, since H-2b/H-2dm1 heterozygotes resemble H-2b homozygotes in their relative resistance to FV; the mutant H-2dm1 haplotype lacks the entire D region of the parental haplotype except for a single class I gene formed by the fusion of its terminal D-region genes to produce a class I gene differing from both parental genes, and thus this finding indicates that one or more D-region genes of the H-2d haplotype can actively suppress H-2b-associated resistance. Unlike H-2dm1, the mutant H-2dm2 haplotype, which retains only the class IDd gene in the D region of the H-2d haplotype, strongly suppresses resistance in H-2b/H-2dm2 heterozygotes, and the presence of Dd as a transgene significantly reduces the resistance of H-2b homozygotes. Since H-2b-associated resistance to FV appears to be due mainly to the capacity of Lb (also called Db), the only class I molecule encoded in the D region of the H-2b haplotype, to present viral epitopes for recognition by FV-specific cytotoxic T lymphocytes, suppression of resistance to FV by the Dd molecule implies that the presence of one class I molecule of the major histocompatibility complex can interfere with either the presentation of viral epitopes by another class I molecule or the generation of T cells that recognize viral epitopes so presented.
Polsky
D
D
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461.
Lilly
F
F
D000818:Animals; D002872:Chromosome Deletion; D005622:Friend murine leukemia virus / Q000276:immunology / Q000472:pathogenicity*; D005805:Genes, MHC Class I; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes; D007942:Leukemia, Experimental / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D013045:Species Specificity; D013163:Splenomegaly / Q000276:immunology
D006183:H-2 Antigens