Immunogenetic studies on the resistance of mice to highly metastatic DBA/2 tumor cell variants. II. Influence of minor histocompatibility antigens on tumor resistance, gamma-interferon induction and cytotoxic response.

B10.D2 mice (H-2d) were found to be able to reject more than 10(6) cells of the DBA/2 (H-2d) tumor ESb, while DBA/2 mice could not reject even small (less than 10(1) cells) tumor cell inocula and died within a few weeks from the developing internal metastases. Chimaeric mice and F1 hybrids between DBA/2 and B10.D2 were susceptible to the tumor and its metastases, suggesting that tumor resistance was dependent on the ability of the host to recognize DBA/2 minor alloantigens. About two thirds of the (DBA/2 X B10.D2) F2 generation mice were ESb tumor-resistant. Also, the majority of C57B1/6 X DBA/2 recombinant inbred strains (BXD RI lines) of H-2d type were found to be able to reject ESb tumor cells. There was no apparent linkage of tumor resistance to coat color genes. Mls locus, or immunoglobulin heavy chain genes. It is suggested that tumor resistance in these mice was dependent on the recognition of several DBA/2 minor histocompatibility antigens such as H-1 and H-4. The most resistant of the BXD RI strains, BXD-6, was shown to react to minor DBA/2 antigens by the production in vitro of interferon and of cytotoxic cells. These cellular immune reactions were not observed in one of the less resistant strains, BXD-28, suggesting a close relationship between tumor rejection and the capability to produce interferon and cytotoxic lymphocytes.