The major histocompatibility complex, H-2 in mouse and HLA in man, probably controls host resistance and immune response to malignancy through numerous mechanisms which we collectively term immune response gene phenomena. In a single widely studied model system called P815 the first six years of this project have demonstrated that two or more genes of H-2 can determine resistance to transplanted P815 in the histocompatible tumor resistance model which depends on the hybrid effect whereby P815 (DBA/2 origin) is relatively resisted by (C57BL/6 x DBA/2)F1 hybrids compared to DBA/2 mice. This B6D2F1 vs D2 difference involves the H-2Kb gene because replacing B6 with a variety of mutants at H-2k?b? can lead to effects ranging from complete loss of the hybrid effect (bm10) to development of super resistance (bm8). The I-A?b? gene is also involved because use of bm12 in place of B6 results in diminished resistance. The hybrid effect can be transferred to thymectomized, irradiated D2 mice with T-cell depleted hybrid bone marrow plus hybrid thymus epithelium. Different determinants are involved in the marrow stem cell and thymus because responder bm8 x D2 thymus epithelium alone fails, while bm8 x D2 stem cells require only that the thymus epithelium is hybrid type (i.e., bm10 x D2 epithelium works but D2 epithelium fails). No genes of the B6 H-2D end or non H-2 are involved. One or more non H-2 genes from C57BL/10 can be involved in the thymus epithelium effect but no non H-2 genes are required in intact animals by studies using RI lines. The objective of the project is to further investigate the immunological and genetic parameters involved in these phenomena. Since B6, bm8, and bm10 differ only by a few amino acids in the H-2K?b? molecule, these studies can add some precision to studies of tumor immunology. (SR)
| Kwak, L W; Grand, L C; Williams, R M (1991) Radiation-induced augmentation of host resistance to histocompatible tumor in mice. Detection of a graft antitumor effect of syngeneic bone marrow transplantation. Transplantation 51:1244-8 |
