Abstract

It was reported previously that a weakly immunogenic antigen that is specific for MM2 ascitic mammary carcinoma cells is converted to a strongly immunogenic one when it is combined with MM2-specific agglutination factor, a galactose-binding protein found in serum from MM2-regressor animals. Such conversion is apparently inhibited in tumorbearing animals, although the factor and antigen-bearing cells are both present. Two glycoproteins, designated as Inhibitors A and B, inhibited this conversion and, therefore, seemed to provide a means for the cells to escape from cytotoxic host reactions. These glycoproteins were isolated from the ascites and serum from MM2-bearing C3H/He mice. They bound to the agglutination factor and competitively inhibited the specific agglutination of MM2 cells in vitro , and they also inhibited specific transplantation inhibition activity of serum from MM2-regressor mice. Unlike the antigen, they did not have immunogenicity even when they were combined with the agglutination factor. Inhibitor B inhibited cell line-specific agglutinations of other cell lines nonspecifically, while Inhibitor A showed some specificity for MM2-specific agglutination. A similar nonspecific inhibitor was obtained by treating the specific antigen with papain. The inhibitors and the antigen had common antigenicity to xenogeneic animals. It was inferred that these inhibitors are produced by sequential degradation by proteolysis of MM2-specific antigen shed from cells (antigen Inhibitor A Inhibitor B). The saccharide moiety of the antigen seems to remain intact in the inhibitors and plays a major but nonspecific role in the binding of inhibitors to the agglutination factor, while the specificity and the immunogenicity of the antigen is dependent on its protein moiety. 1 Supported in part by a Cancer Research Grant from the Ministry of Education of Japan.