Histocompatibility antigens acting as helper determinants for tumor-associated antigens of murine lymphosarcoma.

Abstract

The mechanism of effectiveness of allogeneic versus syngeneic immunization in mounting a humoral specific immune response against tumor-associated antigens of murine urethan-induced thymic lymphosarcomas was studied. C57BL mice immunized with untreated or blocked C3Hf lymphoma cells yielded sera with complement-dependent cytotoxicity for C57BL lymphosarcomas, whereas they did not respond to repeated injections of blocked syngeneic lymphoma cells, indicating a helper activity of alien alloantigens in the reflex of tumor antigens. Thymectomized, lethally-irradiated and T, but not B-reconstituted mice produced active sera, suggesting a T-dependent response. The anti-tumor activity of the serum ran parallel with the anti-histocompatibility one. The tumor-associated and the alien histocompatibility determinants had to be present on the same cell membrane. In addition, active sera were obtained when immunizing syngeneic lymphoma cell inocula were followed by allogeneic normal immunocompetent cells. It is suggested that either a helper mechanism with B and T cells cooperating in recognizing haptenic tumor-associated and carrier histocompatibility antigens or a graft-versus-host reaction determining an abnormal induction of the immune system is needed in order to detect the weak tumor-associated antigens of urethan-induced lymphomas.