Tumor rejection antigens of chemically induced sarcomas of inbred mice

Abstract

Chemically induced sarcomas of inbred mice are immunogenic in syngeneic hosts, and preimmunization with tumor cells leads to resistance to subsequent tumor transplants. The tumor rejection antigens (TRAs) that mediate this reaction are highly specific for each tumor; cross-protection between different syngeneic sarcomas is rare. Isolated membrane and cytosol fractions from two antigenically distinct BALB/c sarcomas, Meth A and CMS5, have TRA activity, and biochemical characterization of the active components from the cytosol and plasma membranes of these two tumors identified a glycoprotein of Mr 96,000. Immunization with unfractionated Meth A cytosol frequently leads to tumor enhancement, but the tumor-enhancing activity (TEA) is lost on fractionation and TRA activity becomes demonstrable. As Meth A and CMS5 lack expression of murine leukemia virus (MuLV) antigens or transcripts, MuLV-related antigens cannot be involved in the TEA or TRA activities of these tumors. In contrast to the lack of cross-reactivity between Meth A and CMS5 TRAs in transplantation tests, rabbit antiserum prepared against the Meth A Mr 96,000 antigen reacted with the CMS5 Mr 96,000 antigen. In view of the biochemical and antigenic similarities of Meth A and CMS5 TRAs, we propose that structurally related but distinct Mr 96,000 glycoproteins are expressed in chemically induced sarcomas and that these molecules are responsible for the individually specific immunogenicity of these tumors.