IMMUNE TOLERANCE AND AN EXTRACELLULAR REGULATORY ROLE FOR BIVALENT ANTIBODY.
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Biomedical subjects
Publications and source records attributed to H N EISEN.
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Dinitrophenyl derivatives of differing molecular weights and degrees of substitution have been contrasted with respect to their ability to elicit immediate type allergic responses and their capacity to induce antibody formation in the guinea pig. In contradistinction to dinitrophenyl-proteins, bis-DNP-lysine and DNP-polylysines (including a 100,000 molecular weight derivative) failed to induce antibody detectable by guinea pig passive cutaneous anaphylaxis. Dinitrophenyl-polylysines evoked urticarial responses non-specifically, but after succinylation were about as effective as dinitrophenyl-proteins in eliciting specific cutaneous reactions. An important factor influencing the effectiveness of bis-DNP-lysine in evoking specific wheal-and-erythema responses is antibody affinity for the dinitrophenyl-lysyl determinant.
A number of penicillenate and penicilloyl derivatives potentially useful in the study of penicillin hypersensitivity have been prepared and some of their properties described.
Multifunctional derivatives of penicillenic acid are effective elicitors of wheal-and-erythema skin responses in humans allergic to penicillin. Of the effective derivatives, penicilloyl-polylysines are particularly attractive as skin test reagents because they appear to be incapable of inducing antibody formation. The skin responses are specifically inhibitable in most instances by homologous unifunctional haptens. The penicillenic acid derivatives which appear to be determinants of human allergic reactions to penicillin are: penicilloyl, penicillenate, and groups of the penamaldate-penilloaldehyde type. Of these, the most significant appears to be the penicilloyl-lysyl determinant.
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Injection of rabbits with Freund's complete adjuvant containing bovine gamma-globulin substituted to near saturation with dinitrophenyl groups leads to the production of large amounts of antibodies specific for the 2,4-dinitrophenyl substituent. These antibodies can be isolated from sera in satisfactory yield (40 per cent) and in a high state of purity (90 per cent specifically precipitable). Hapten dissolution, which was used to screen haptens for their potential usefulness as specific reagents in the purification procedure, provides a means for evaluating, in relative terms, antibody-hapten affinities (in competition with antigen).