Relative importance of viral and neoantigens in cytotoxic reaction against murine leukaemia cells.

Monkeys and mice were immunized with Rauscher murine leukaemia virus. Two types of leukaemia virus preparations were used as immunogens. One preparation was derived from viraemic plasma and was highly purified by density gradient ultracentrifugation. The other preparation of Rauscher virus was derived from spleen cells and was contaminated with cell membranes. Following immunization with each of these preparations sensitive techniques were utilized to measure antiviral and antileukaemia cell (cytotoxic') antibody levels on aliquots of the same antiserums. Multiple serums from each animal were tested during the weeks of immunization in order to establish a parallelism or lack of parallelism in the changes in cytotoxic and antiviral antibody levels. In each antiserum the cytotoxic and antiviral titres were virtually the same. This was true whether the animal had been immunized with a purified or a non-purified virus preparation. The presence or absence of contaminating cell membrane material in the immunizing material did not result in an antiserum with increased or decreased cytotoxic to antiviral antibody ratio. This indicated that cytotoxic antibody is probably not the result of immunization against cell membrane antigens (neoantigens') as distinguished from virus or virion subunit antigens. Conversely, we found that leukaemia cells containing relatively little virus did not lyse in the presence of cytotoxic antibody prepared against either membrane-rich or membrane-poor virus preparations. This finding suggests that virus and not independent neoantigen renders the leukaemia cell lysable by cytotoxic antibody. Our studies therefore minimize the significance and even question the presence of neoantigens in Rauscher leukaemia cells, since the cytotoxic capability of anti-Rauscher antiserum is dependent on the presence of virus and not neoantigen in the immunizing preparations, and since virus and not neoantigen renders the infected cell lysable by anti-Rauscher antibody.