Structure and expression of genes encoding murine Qa-2 class I antigens (major histocompatibility complex)

DNA structural analysis of the Qa region in two BALB/c mouse substrains with different Qa-2 phenotypes reveals that a deletion of DNA has occurred in BALB/cBy (Qa2^-) mice relative to BALB/c (Qa2⁺) mice. We propose that this deletion arises from unequal crossing-over and recombination between adjacent BALB/c class I genes and results in the generation of a hybrid class I gene in BALB/cBy mice. Furthermore, we suggest that this is a direct cause of the change in Qa-2 phenotype. Further support for this model was obtained from transfection experiments in which cloned genes from the equivalent part of the Qa region inC57BL/10 mice were introduced into L cells. Four C57BL/10 genes, arranged in two almost identical pairs, encode polypeptides that are precipitated from lysates of transfectants with anti-Qa-2/3 antiserum. Although loss of one pair of these genes in BALB/c mice has no qualitative effect on Qa-2 phenotype, the loss of both pairs of genes via gene fusion leads to the loss of the Qa- 2⁺ phenotype in BALB/cBy mice.