Induction of immunological tolerance to the penicilloyl antigenic determinant—iv. The effect of BPO-oligolysines and cholestanol-bearing BPO-oligolysines on murine IgE responses

Abstract

Penta-, deca- and eicosalysine carriers were synthesized in solution and conjugated with benzylpenicillin to give BPO-conjugates of high haptenic density. Each oligolysine conjugate was prepared in two forms—with a free C-terminus and with an esterified C-terminus carrying via a benzylester bridge in essence a lipophilic cholestanol moiety [ p-moxymethylbenzylcholestan-3β-yl succinate (OSuco group)]. Decalysines that carried a single haptenic BPO group and succinyl groups on the other amino functions were also prepared. Suppression of IgE responses was studied in BALB/c mice. It was found that BPO-specific suppression could be induced by injecting OSuco-bearing deca- or eicosalysine conjugates before immunization with BPO-Asc in A1(OH) 3. The pentalysine conjugate was only slightly effective as were all OSuco-deficient conjugates. Ongoing IgE responses were only slightly suppressed and OSucobearing conjugates were not more effective than OSuco-deficient derivatives. When the monohaptenic OSuco-bearing decalysine, which exhibited weak tolerogenic effects on primary as well as on ongoing responses, was applied under conditions that favour suppressor T-cell induction, a pronounced unresponsiveness resulted. Direct evidence for suppressor T-cell involvement in the abrogation of anti-BPO responses by OSuco-bearing BPO-conjugates was obtained from cell transfer experiments. The study shows that relatively small haptenic conjugates, the lower limit of effectiveness being approximately represented by decalysine conjugates, may be effective tolerogens depending on the immune status.