Ability of H-2 regions to induce graft-vs-host disease

Individual young adult F1 hybrid mice were irradiated with 500 R and 24 hr later injected with 5 X 10(7) spleen cells obtained from a sex-matched parental-strain donor. The injected animals were then followed for a period of 3 months and loss of body weight, mortality rate, and other signs of fatal graft-vs-host disease (GVHD) were recorded. The donor-recipient strain combinations were selected in such a way as to provide genetic differences in the entire H-2 complex, the K or D regions alone, the K or the D end, and the central (I) regions alone. The data obtained on only few combinations indicate that strong GVHD (100% mortality rate within the first month after the injection) occurs only in those donor-recipient combinations which differ in the entire H-2 complex or in the K end (K + I regions). Much weaker GVHD (mortality rate of only 50% or less and death of individual mice spread over the entire observation period) is observed when the donor and the host differ in either the K, I, or D region alone. The degree of GVHD induced by three regions, when taken singularly, is about the same. Surprisingly, the K-region GVHD was somewhat stronger in combinations of mutant strains in comparison with recombinant-strain combinations.