Effects of genetic background on transmission of incompatibility resulting from mutant minor histocompatibility genes.

A mutant minor histocompatibility gene, H(KH-11), was earlier reported to be unable to generate a skin allograft response unless the graft donor carried both the mutant gene and H-2Db. H(KH-11) and H-2 are unlinked, so animals heterozygous at the two relevant loci transmitted the mutant phenotype to only 25% of their progeny when backcrossed to an appropriate partner, although 50% actually inherited the mutant gene. To examine the generality of the requirement for multiple loci to generate graft incompatibility, we investigated the transmission of mutant (incompatible) phenotypes for 24 different mutant non-H-2 histocompatibility genes. Approximately half the mutant phenotypes were transmitted in frequencies suggesting that multiple loci may be involved. In certain cases, an individual mutation was transmitted at different frequencies when backcrossed onto different inbred strain backgrounds--as if the mutant phenotype were due to a single segregating locus on one background, but required two unlinked segregating loci on another. In cases in which multiple loci were involved, the relevant H-2 complex often seemed to be coselected in the backcross progeny along with the mutant minor H-gene.