The genetic structure of the H-2 system has been traditionally interpreted as consisting of multiple regions controlling histocompatibility antigens. Recently however, many difficulties have been encountered in attempts to construct a single, consistent linear H-2 map on this basis. We have shown that the genetic, serological, and biochemical findings on the H-2 system can be more readily explained by the assumption that there are only two histocompatibility regions (loci) in the H-2 system, H-2D and H-2K, which are separated by loci controlling serum proteins (Ss-Slp), immune response (Ir-1), and perhaps others. Evidence supporting such an interpretation of the H-2 system was obtained by a transplantation analysis of the 14 well-defined H-2 crossovers. F1 hybrids between different H-2 crossovers were produced and challenged with skin grafts from third party strains. The donor-recipient relationships in these combinations were such that in at least 10 cases the skin grafts should have been rejected if the multiple-region H-2 map is correct but should survive permanently if the two-region model is correct. In all instances, the skin grafts survived permanently, providing further evidence for the two-region map of the H-2 complex.

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