Suppression of antibody responses by conjugates of antigens and monomethoxypoly(ethylene glycol)

Abstract

Some of the studies employing non-antigenic, non-allergenic and tolerogenic derivatives of antigens and allergens, synthesized by coupling onto them an optimal number ( n) of molecules of monomethoxypoly(ethylene 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 Thy1-2 +, CD3 +, CD4 −, CD5 −, CD8 + and expressed the αβ-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 α-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.