Antibody responses to the penicilloyl (BPO) group, the major antigenic determinant of penicillin allergy induced in C3H mice by penicilloylated bovine gamma globulin in complete Freund's adjuvant, were reduced or abolished by various amino acid polymers and copolymers of different composition and size carrying BPO groups. Tolerogenic treatment was effective before or after primary immunization and also during anamnestic responses. The unresponsive state was of long duration and persisted even after several booster injections when efficient tolerogens were used. Among the most promising tolerogens are fully penicilloylated oligolysines with a molecular weight below 10 000.
A specific tolerant state to the major antigenic determinant of penicillin allergy, the penicilloyl group, was induced in C3H mice primarily immunized with penicilloylated bovine gamma globulin in complete Freund's adjuvant. Tolerance was obtained by intraperitoneal administration of either of two penicilloyl-bearing dextrans of molecular weight 2 X 10(6). One conjugate contained penicilloyl groups stably bound via a 1,6-diaminohexane spacer, the other bore the penicilloyl groups directly bound to the hydroxyl groups of the carrier. These directly bound penicilloyl groups undergo hydrolytic cleavage within 3 days under physiological conditions in neutral aqueous solution. Model experiments showed that the rapid cleavage into carrier and haptenic derivatives also applies to penicilloylated dextran in receptor-bound and particulate form, as may be expected from the highly hydrophilic character of the conjugate. The stable conjugate at 1 mg and the cleavable conjugate at 4 mg doses induced comparable tolerance lasting for at least 8-12 weeks.
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