Chemically induced sarcomas of inbred mice are characterized by the expression of individually distinct tumor-specific transplantation antigens (TSTA). This research centers on the serological analysis of the cell surface antigens of chemically induced sarcomas with monoclonal antibodies. The major objective is to isolate antibodies with specificity to the individually distinct tumor-specific antigens as an approach to defining the molecular basis of the observed antigenic polymorphism of this class of tumor antigen and its role in transformation. To date, two monoclonal antibodies, HD62 and HD339, with reactivity to the BALB/c Meth A sarcoma have been isolated. Absorption analysis of 21 chemically induced BALB/c sarcomas indicates that expression of the HD62 antigen is restricted to Meth A, while the HD339 antigen is detected on three sarcomas, Meth A, CMS1, and CMS21. Neither antigen is detectable on a wide range of leukemiaa, normal lymphoid tissues, or normal adult lung fibroblasts. The HD339 antibody precipitates from cell-free extracts of either I?125?-surface labeled or S?35?-methionine labeled Meth A cells, an 86-kilodalton glycoprotein. Our immediate research aims are the isolation and characterization of HD339-86-kilodalton Meth A antigen. The antigen will be purified by a combination of gel filtration and affinity chromatography. The presence of the HD339 antigen will be monitored by the ability of chromatography fractions to block the binding activity of the HD339 antibody. The chromatography fractions will also be Assayed for their ability to block the cytotoxic activity of the HD62 antibody, the p75 Meth A antigen as defined by rabbit antisera, and Meth A tumor protection activity (Meth A TSTA). This comprehenaive analysis should put into perspective the role of the serologically defined tumor-specific cell surface antigens (HD62, HD339) and the Meth A TSTA as defined in tumor rejection assays. (AG)
