Induction of immunological tolerance to the penicilloyl antigenic determinant. I. Evaluation of penicilloylated amino acid polymers and copolymers in mice

Abstract

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.

The Use of Hapten-Polysaccharide Conjugates for the Induction of B-Cell Tolerance Involving IgE Responses

“…Persistence of T-independent antigens in the animal is usually cited as playing a role in mainte nance of tolerance [Klaus et al, 1976] and a more thorough investigation of the rate at which species eliminate different tolerogens would help in the search for the most suita ble ones. While the carrier, polysaccharide or otherwise, may act merely as a backbone for the hapten, evidence is accumulating that it plays some non-specific role in the induction of tolerance [Vidal-Gomez, 1978], The extensive studies performed by Otz et al [1978] with different carriers would tend also to support this view. These two concepts, persistence and non-specific activity of the carrier, lead us to suggest that tolerance induction can be optimized not only by increasing the degree of hapten-sub stitution but also by selecting the ideal car riers for the particular species under study.…”

An Evaluation of Receptor‐Mediated Gene Transfer Using Synthetic DNA‐Ligand Complexes

“…Poly(1-lysine) has been shown to induce a T-cell-independent immunological response when injected into animals [58, 591. In contrast, poly(1-lysine) bound to an antigen can induce tolerance to that antigen [60] [61] showed that when poly(Llysine) is added to two different populations of DNA containing either GC-rich or AT-rich regions, an insoluble complex is formed, composed exclusively of the AT-rich fraction of the DNA present in the solution. In contrast, poly(L-arginine) binds preferentially to GC-rich DNA.…”

Induction of Immunological Tolerance to the Penicilloyl Antigenic Determinant

“…In this respect, the BPO determinant coupled to the copolymer of D-glutamic acid and D-lysine [1], syngeneic immunoglobulins [2], and to a variety of polysaccharides and amino acid polymers [3,4] have been successfully evaluated. Cleavable penicilloylated dextrans as evalu ated previously [5] and in this study possess some particular assets not found among the other tolerogens.…”

“…with BPO bovine gammaglobulin in com plete Freund's adjuvant [4,5], Since IgE class antibodies have been shown to play an important role in immediate hypersensitivity [6], the present experiments were carried out to evaluate the suppressive effect of cleavable BPO-DEX on BPO-specific IgE antibody formation using BALB/c and C3H mice and an immunization schedule partic ularly suited for induction of IgE responses.…”