Reactivity of contact allergenic haptens to amino acid residues in a model carrier peptide, and characterization of formed peptide-hapten adducts

Abstract

The type of chemical reaction between hapten and carrier protein in the formation of a complete antigen in vivo giving rise to an allergic contact dermatitis (ACD, type IV allergy) is essentially unknown. About 4000 low-molecular organic compounds are known to have allergenic properties. alpha,beta-Unsaturated carbonyl structures are frequently present among these compounds. Haptens giving rise to antibody formation and type I allergy have been shown to add predominantly to lysine in the carrier protein. In this paper, the reactivity of activated type IV haptens to a model peptide is reported. Essentially all amino acids with nucleophilic properties were present in the model peptide. Investigation of the relative reactivities of the amino acid residues to activated haptens under biomimetic conditions is performed in order to determine the proportions between the adducts of the different amino acid moieties. In all cases, the electrophilic alpha,beta-unsaturated haptens were found to be added to the cysteine residue and no lysine adduct was recorded. Nuclear magnetic resonance (NMR) spectroscopy was used to exclude steric hindrance of any amino acid residue in the addition reaction. The hapten-modified peptides were isolated and characterized by NMR and mass spectrometry.