The Role of HSP90 in Tumor Specific Immunity

Abstract

Tumors induced by chemical carcinogens usually express tumor specific transplantation antigens (TSTAs) (Law etal., 1980; Law,1985). These antigens are defined by their ability to induce tumor specific immunity when syngeneic hosts are preimmunized with irradiated tumor cells or cellular fractions containing the tumor specific antigens. An important characteristic of TSTAs, is that upon challenge with tumors the induced immunity is confined to the original tumor and not other independently derived syngeneic tumors. The immune response to these antigens is, for the most part, limited to a cellular immune response. However, under certain conditions of hyperimmunization, tumor specific cytotoxic sera have been developed in syngeneic hosts (De Leo etal., 1978). The ability of these proteins to act as antigens is probably due to a molecular change(s) in the protein, such as a missense mutation or altered post translational processing of the tumor antigen. Other mechanisms could potentially induce immunogenicity, such as expression of a normally silent gene or an alternative splicing mechanism. However, it is difficult to envision how these latter mechanisms could generate the extensive diversity of TSTAs. The goal of the research discussed here was to purify and identify these TSTAs and to determine the molecular change which rendered these proteins immunogenic and tumor specific.