Carl Prausnitz Memorial Lecture. Suppression of antibody responses by chemically modified antigens

Some of the studies employing nonantigenic, nonallergenic and tolerogenic derivatives of antigens and allergens, synthesized by coupling onto them an optimal number (n) of molecules of monomethoxy-polyethylene glycol (mPEG), are briefly reviewed. Administration of antigen (mPEG)n conjugates into mice resulted in specific immunosuppression, which was mediated by antigen-specific suppressor T (Ts) cells and by suppressor factor(s) (TsF) produced by these cells. These Ts cells were cloned and shown to be Thy-1.2+, CD3+, CD4-, CD5-, CD8+, and expressed the alpha beta heterodimer of conventional T cell receptors (TCR). The TsF had the functional activity of Ts cells and possessed at least one epitope related to the alpha-chain of TCR. The results of clinical trials of mPEG conjugates of common allergens are briefly referred to; it is suggested that the time is opportune for the evaluation of the therapeutic efficacy of mPEG conjugates of pure allergens which can be synthesized on an industrial scale by recombinant DNA technology. Finally, possible applications of tolerogenic mPEG conjugates of xenogeneic monoclonal antibodies, immunotoxins and immunogenic recombinant lymphokines to the development of immunotherapeutic strategies in oncology, transplantation, autoimmunity and acquired immunodeficiency syndrome are discussed.