Tumor-specific transplantation antigen: use of the Ad2+ND1 hybrid virus to identify the protein responsible for simian virus 40 tumor rejection and its genetic origin.

Cells transformed by simian virus 40 (SV40) possess a tumor-specific transplantation antigen (TSTA) that has the property of immunizing animals against syngeneic tumor challenge. We find that the early SV40 DNA segment present in the human adenovirus 2 (Ad2)-SV40 hybrid, Ad2+ND1, is sufficient to induce this SV40-specific TSTA in BALB/c mice. Moreover, studies on the intracellular distribution of TSTA activity in Ad2+ND1-infected cells, as determined by the ability of various subcellular fractions to immunize mice against syngeneic tumor challenge, have suggested a correlation between this biological activity and the presence of the SV40-specific 28,000Mr protein in coded by this hybrid virus. Both the TSTA activity and the 28,000 Mr protein are found in the plasma membrane fraction and in the perinuclear region of infected cells but are virtually undetectable in the cytoplasmic fraction. Using a hamster antitumor antiserum that can specifically immunoprecipitate the 28,000 Mr protein, we are able to demonstrate a loss of TSTA activity concomitant with the removal of this SV40-coded protein. Thus, it appears that antigenic determinants responsible for SV40-specific tumor rejection in mice are contained within the 28,000 Mr protein coded for by the early SV40 DNA segment that extends from 0.17 to 0.28 map unit.