Immediate hypersensitivity to drugs and simple chemicals: the efficacy of monovalent elicitors

• Published in: European journal of immunology Vol. 15; no. 2; p. 155
• Main Authors: Schneider, C H, Guenin, R, Toffler, O
• Format: Journal Article
• Language: English
• Published: Germany 1985
• Subjects: Animals; Dinitrophenols - immunology; Epitopes; Guinea Pigs; Haptens; Hypersensitivity, Immediate - immunology; Oligopeptides - immunology; Receptors, Immunologic - immunology; Structure-Activity Relationship
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830150209

Introduction of a reactive monohaptenic chemical into the sensitized organism will not normally result in elicitation of immediate reactions. Rather, the first products of chemical conjugation to suitable carriers in vivo are monohaptenic, conjugates which are inhibitory according to the bridging concept, stating that the initiating event for mast cell and basophil activation is a cross-linking of membrane-bound antibody by dihaptenic or oligohaptenic antigen. Simple calculations and quantitative data are presented to show that built-in inhibition is indeed a powerful barrier to any rapidly occurring allergenic manifestation which depends on the formation of divalent conjugates. If and when such a reaction does nevertheless occur, special requirements have to be invoked. One possibility is that the chemical or drug as such, i.e. without conjugation to a carrier, is an elicitor of anaphylaxis. Such compounds are known in a guinea pig passive cutaneous anaphylaxis model system, but there is evidence that they may also play a role in clinical situations. These monovalent elicitors possess in addition to the haptenic moiety an auxiliary group. The auxiliary group requirements were studied in the guinea pig passive cutaneous anaphylaxis system by using synthetic peptides with an N-terminal 2-carboxy-4,6-dinitrophenyl group as the hapten and phenylalanine and modified phenylalanine at the C-terminus as auxiliary group. The conclusions are that effective auxiliary function depends on the benzene ring and neighboring carboxyl groups in selected positions. Anaphylactogenicity is high when the haptenic and auxiliary groups can act independently, i.e. when separated by a peptide chain of considerable length. Potent anaphylactogens with close linkage of the two groups have, however, also been found. It is unlikely that the passive cutaneous anaphylaxis elicitations observed here are mediated by some form of indirect bridging of membrane-bound antibody.