Hybrid resistance to the C57BL lymphoma EL-4 and to two 3-methylcholanthrene-induced B10.A(4R) fibrosarcomas of recent origin was studied in H-2 heterozygous mice. Histocompatible tumor recipients were derived from mating C57BL/10, B10.A, and H-2a/H-2b intra-H-2 recombinant mice in such a way as to provide heterozygosity at defined portions of the H-2 complex. Hybrid resistance was assessed by comparing the mean survival times and tumor incidence of H-2 heterozygotes with those of homozygous 4R (sarcomas) or B10 (EL-4) mice. The results reveal that heterozygosity at the D end of the H-2 complex controls hybrid resistance to fibrosarcomas as well as to lymphomas. Evidence is discussed which suggests that the locus controlling hybrid resistance, Hh-1, is located within the H-2 complex between the S and D regions. Hh-1-controlled hybrid resistance was clearly demonstrable when tumor cells were inoculated by the intraperitoneal route but was not detected if tumor cells were injected subcutaneously. Both Hh-1-controlled hybrid resistance and its in vitro correlate, natural cytotoxicity, appear to be most strongly expressed in the peritoneum. Pretreatment of Hh-1 heterozygous mice with Hh-1-H-2Db parental spleen cells consistently reduced tumor resistance compared to mice pretreated with reciprocal parental Hh-1-H-2Dd splenocytes. This suggests that Hh-1 codes for or regulates the expression of cell-surface antigens found on normal H-2b parental cells. In addition, we have found that other H-2 genes, probably I region immune response genes, also influence fibrosarcoma growth in F1 hybrid hosts. Thus, several loci within the H-2 complex appear to play a role in the polygenic control of the immune response to fibrosarcomas.


This work was supported by National Institutes of Health Grants AI-13870 and CA-15788 and by University of California Cancer Research Coordinating Committee Grant 76LA9.

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