Cytotoxic T cell lysis of H-2-negative murine sarcoma cells

The DOH cell line was established from C3H.OH (H-2Kd,Dk) embryonic fibroblasts transformed with Rous sarcoma virus (RSV) in vitro. When injected into syngeneic mice, DOH cells were very weakly tumorigenic and induced a cytotoxic immune response. Cytotoxic T lymphocytes (CTL) specifically lysed DOH cells but not other RSV-induced sarcoma cells, which shared the H-2Kd or H-2Dk antigen, respectively, with DOH. Serological and immunochemical analysis of H-2 antigens subsequently showed that DOH sarcoma cells did not express syngeneic H-2K and H-2D antigens. Surprisingly, a H-2Kk-specific monoclonal antibody (100-5) bound to DOH cells and was inhibitory for syngeneic CTL specific for DOH. In addition, DOH cells were lysed by alloreactive H-2Kk-specific CTL. The demonstration of immunogenic H-2-negative sarcoma cells suggests that either the H-2K antigens have been extensively altered or that hitherto unidentified major histocompatibility complex class I molecules are expressed on DOH sarcoma cells surfaces, acting as target antigens for tumor-specific CTL.