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H-2-linked genetic control of resistance to histocompatible tumors
Abstract:
The role of the major histocompatibility complex of the mouse (H-2) in resistance to two transplanted histocompatible tumors was evaluated by determining the differences in survival times between the syngeneic parent strain and various F1 hybrids. C57BL/10nSn (B10) mice and their F1 hybrids were given injections of a methylcholanthrene-induced fibrosarcoma of B10 origin. The B10 x B10.BR F1, B10 x B10.M F1, B10 x B10.WB F1, and B10 x 5R F1 hybrids survived significantly longer than the B10 parental strain or B10 x B10.D2 F1 and B10 x 18R F1 animals, while B10 x 2R F1 mice succumbed significantly sooner than any of the above groups. Statistical comparisons of geometric mean survival times of the strain of tumor origin (B10) versus the F1 hybrids showed the influence of genes coded for the H-2 complex in the phenomenon, termed "hybrid resistance" or "allogeneic inhibition." However, tumor resistance did not occur in all hybrids and could not be attributed to a single dominant Ir gene localized in the I region as might be predicted if the phenomenon involved genetic control of immunological responsiveness to tumor-specific transplantation antigens. Similarly, in a second group of experiments, the mean survival times of DBA/2 x B10.D2 F1 animals given injections of the 815 mastocytoma of DBA/2(D2) origin was compared to the mean survival times of various hybrids with the D2 parent. Again, the results demonstrated the importance of the H-2 gene complex in this phenomenon. However, the above results did not permit precise localization of the H-2-linked gene(s) responsible for differential resistance to the histocompatible tumor.
Insights
The mouse major histocompatibility complex (H-2) influences resistance to transplanted tumors, affecting survival times in F1 hybrids. This "hybrid resistance" is linked to H-2 genes but not solely to immune response genes.
Area of Science:
- Immunology
- Genetics
- Oncology
Background:
- The major histocompatibility complex (MHC) plays a crucial role in immune responses.
- Understanding MHC's role in tumor rejection is vital for cancer research.
- Hybrid resistance, or allogeneic inhibition, is a phenomenon observed in F1 hybrids challenged with parental tumors.
Purpose of the Study:
- To investigate the role of the mouse major histocompatibility complex (H-2) in resistance to transplanted tumors.
- To determine if specific H-2 genes influence survival times in F1 hybrid mice bearing syngeneic tumors.
- To explore the genetic basis of hybrid resistance and its relationship to immune response genes.
Main Methods:
- Transplantation of chemically induced tumors into syngeneic mice and their F1 hybrids.
- Comparison of survival times between parental strains and F1 hybrids.
- Statistical analysis of geometric mean survival times to assess H-2 complex influence.
Main Results:
- F1 hybrids exhibited differential survival times when grafted with parental tumors, indicating H-2 gene influence.
- Hybrid resistance was observed, but not universally across all hybrids, suggesting complex genetic control.
- The phenomenon could not be solely attributed to a single dominant immune response (Ir) gene in the I region.
Conclusions:
- The H-2 gene complex is a significant factor in hybrid resistance to histocompatible tumors.
- The genetic control of this tumor resistance is complex and not solely dependent on immune response genes.
- Further research is needed to precisely localize the specific H-2-linked genes responsible for differential tumor resistance.