Serologic analyses of antisera raised in mouse strain combinations differing at the major histocompatibility complex

Serologic analyses of antisera raised in mouse strain combinations differing at the major histocompatibility complex (H-2) indicate that each H.2 haplotype is characterized by numerous antigenic specificities. It has been proposed that the data are most easily explained in terms of two tightly linked loci, H-2K and H2D (1-3). This "two-gene" model implies that the product of each H-2K or H-2D region bears several alloantigenic specificities. Antigenic specificities unique for a single H-2K or H-2D region, or regions presumed to be of a common origin, have been designated "private" specificities, while antigenic specificities shared between different regions or different alleles of a region have been designated "public" specificities. The molecules determined by the H-2K and H-2D region are glycoproteins of an apparent mol wt of 45,000 daltons. Cullen et al. (4) analyzed the soluble H-2 molecules by coprecipitation with various antisera and demonstrated that, in the combinations tested, each H-2K or H-2D product bore private and public specificities. This was also demonstrated by lymphocyte redistribution studies in several strains (5, 6). After reviewing the data for and against the two-gene model, Klein noted that the great preponderance of data supported the model (7). Recently, however, co-capping (8) and immunoprecipitation techniques (9) have suggested that antisera to private and antisera to public specificities detect two separable molecules associated with the D region of the H-2 ~ haplotype. An additional approach to the question of the number of genes associated with the D d region recently became possible through the discovery of the BALB/c, H2 loss mutant, designated BALB/c-H-2 ~° (10). Skin from BALB/c was quickly rejected by the mutant (11-12 days), but grafts in the opposite direction survived indefinitely. No serological differences were detectable between wild type and mutant with the notable exception that the mutant did not react with one antiserum detecting public H-2 specificities (11). However another antiserum presumably of similar specificity reacted equally well with both strains. Skin graft complementation studies localized the antigenic loss of the BALB/c-H-2 db mutant to the D end of its H-2 haplotype (11). Since the mutation occurred in an H-2 d strain and since recent precipitation studies from this laboratory (9)