HYBRID Ia MOLECULES ON RETICULUM CELL SARCOMAS

The reticulum cell sarcoma (RCS) 1 of S JL / J mice has been shown to express alien histocompatibility membrane antigens (1, 2). This form of tumor antigen is, by definition, present on cancerous, but not normal, syngeneic tissues. However, it differs from other forms of tumor-associated antigens because it is a normal membrane component of one or more strains allogeneic to the host (3). In the case of the RCS, both antibody and cytotoxic lymphocytes directed against syngeneic H-2 s or allogeneic H-2 a determinants react strongly with an in vitro cultured RCS. Weak reactivities with anti-H2 b cytotoxic lymphocytes have also been seen in these neoplasms. In contrast to the results found with the in vitro cultured RCS lines, in vivo passaged lines have previously shown no detectable alien histocompatibility antigens as recognized by specific cytotoxic lymphocytes. Furthermore, specific antibody could detect only specificities of the H-2 a haplotype and no H-2 b specificities (1). An additional trait of the RCS is that it readily induces a syngeneic host immune response (4). Proliferation of Ly 1+23 T lymphocytes can be induced in mixed lymphocyte-tumor in vitro cultures (5). Lymphocytes can also be induced to proliferation in vivo by immunization with irradiated tumors (6). Specific cytotoxicity against the tumor has been demonstrated when the in vitro RCS lines are used as stimulators in mixed lymphocyte-tumor cultures and as targets in cytotoxic assays (1). In addition, syngeneic T lymphocytes have been induced to cytotoxicity against in vivo passaged RCS by special hyperimmunization regimens (7). In primary mixed lymphocyte-tumor cultures, in vivo passaged RCS and spontaneous RCS have been shown to induce only T lymphocyte proliferation and no detectable cytotoxicity. Little is known of the antigenic determinants on the RCS that are involved in the host anti-tumor immune response. Earlier work found that antisera directed against syngeneic IA-encoded products (i.e., anti-Ia.4) could inhibit the S j L / j anti-RCS proliferative response. This suggested that host responsiveness was induced via interaction with syngeneic Ia molecules (8). In that study, an in vivo passaged RCS was used, so there was no detectable cytotoxicity by the anti-tumor effector lymphocytes. Conversely, another investigation found that syngeneic anti-RCS cytotoxic lympho-