Induction if immunological tolerance to the major antigenic determinant of penicillin: a therapeutic approach to penicillin allergy.

High titered IgE, IgG, and IgM antibody responses to the major antigenic determinant of penicillin, the benzylpenicilloyl hapten, were elicited by the intraperitoneal injection of the hapten coupled to keyhole limpet hemocyanin mixed with the appropriate adjuvant. However, treatment of such mice with the benzylpenicilloyl derivatized synthetic copolymer of D-glutamic acid and D-lysine, either before or after primary immunization, resulted in significant suppression of the subsequent anti-benzylpenicilloyl antibody responses of the IgE and IgG classes, as measured at the humoral and cellular levels. The state of tolerance induced by benzylpenicili-poly(DGlu, Lys) was highly specific, of long duration, and could be induced in a manner that would be appropriate for clinical use. These results provide a direct demonstration of the potential application of the poly(DGlu, Lys) immunotherapeutic approach to penicillin allergy in humans.