Our goals are to develop serological probes to the individually distinct transplantation antigens of chemically induced sarcomas of mouse origin, in order to define their molecular basis and relationship to chemical carcinogenesis. We plan to continue our serological analysis of cell surface antigens of chemically induced sarcomas with emphasis on generating mouse and rat monoclonal antibodies to the individually distinct tumor antigens of recently induced sarcomas. A close relationship between the serologically defined tumor-specific surface antigen (TSSA) of the Meth A sarcoma and its individually distinct transplantation antigen (TATA) has been established. The genes responsible for expression of the Meth A TSSA have been mapped to the same region on chromosome 12 that encodes the immunoglobin heavy chain (Igh) gene cluster. This finding led to speculation that the highly restricted tumor antigens are products of a multigene family and that the genetic elements responsible for Ig idiotypes may also generate the antigenic diversity of tumor-specific antigens. The individually distinct TATAs of two antigenically unrelated BALB/c sarcomas, Meth A and CI-4, have been purified and shown to be 75K proteins with similar biochemical characteristics. The purified Meth A and CI-4 75K TATAs will be used to prepare and isolate rat and mouse monoclonal antibodies with group and restricted specificity. These reagents will be used to isolate additional TATAs and define the antigen-structure relationships of these molecules. The serological reagents generated from these studies will be used to identify and isolate, by DNA-mediated gene transfer techniques, the genes responsible for expression of the individually distinct tumor antigens and define their role in cellular transformation.
NIH ExPorter
NIH ExPorter