Characterization of the spontaneous mutant H-2K^bm29 indicates that gene conversion in H-2 occurs at a higher frequency than detected by skin grafting

A spontaneous mutation of H-2K^b, K^bm29, was discovered among the progeny of F₁ hybrid parents. Unlike other characterized spontaneous class I variants, this mutant was detected with the use of antibody, rather than tissue grafting. Although K^bm29 is serologically indistinguishable from the previously described mutant molecule K^bm3, it is identical to the parental K^b by skin grafting and CTL assays. A full length cDNA of K^bm29 was amplified by polymerase chain reaction with locus-specific primers, cloned, and sequenced. Two nucleotides were found to be mutated, resulting in a single amino acid change (Lys → Ala) at amino acid 89 of the mature glycoprotein. This is consistent with the observed serologic changes, as the same amino acid substitution is responsible for the serologic profile of K^bm3. The occurrence of a mutation which is not detectable by the methods normally used to screen for H-2 mutants provides evidence that the high spontaneous rate of structural mutation described for the K^b molecule is underestimated.