Mechanism of allergic cross-reactions--I. Multispecific binding of ligands to a mouse monoclonal anti-DNP IgE antibody.
A recently developed solid-phase binding assay was used to investigate the specificity of ligand binding to a mouse monoclonal anti-dinitrophenyl IgE [IgE(aDNP)]. All DNP-amino acids, that were tested, inhibited the binding of radio-labeled IgE(aDNP) to DNP covalently attached to polystyrene microtiter plates; however, the concentration for 50% inhibition varied within four orders of magnitude, DNP-L-serine being the most, DNP-proline the least potent inhibitor. In addition to DNP analogues a large number (2074) of drugs and other compounds were tested for their ability to compete with DNP for the binding site of IgE(aDNP). At the concentrations used for screening 59% of the compounds had no significant inhibition; 19% inhibited the binding of IgE(aDNP) more than 50%. Several families of compounds (tetracyclines, polymyxines, phenotiazines, salicylates and quinones) of effective competitors were found. Within these families change in the functional groups attached to the "family stem" had major effects on the affinity of ligand binding. The occurrence frequencies of interactions of ligands with IgE(aDNP) is in good agreement with a semi-empirical model for multispecific antibody-ligand interactions.
Varga
J M
JM
Department of Dermatology, University of Innsbruck, Austria.
Kalchschmid
G
G
Klein
G F
GF
Fritsch
P
P
D000596:Amino Acids / Q000276:immunology; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D002934:Cinnamates / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004140:Dinitrophenols / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004342:Drug Hypersensitivity / Q000276:immunology*; D005664:Furazolidone / Q000276:immunology; D006923:Hymecromone / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism; D066298:In Vitro Techniques; D007216:Indoprofen / Q000276:immunology; D007783:Lactones / Q000276:immunology; D027501:Monocarboxylic Acid Transporters; D010093:Oxolinic Acid / Q000276:immunology; D010640:Phenothiazines / Q000276:immunology; D011113:Polymyxins / Q000276:immunology; D011809:Quinones / Q000276:immunology; D013754:Tetracyclines / Q000276:immunology
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D002934:Cinnamates; D004140:Dinitrophenols; D007783:Lactones; D027501:Monocarboxylic Acid Transporters; D010640:Phenothiazines; D011113:Polymyxins; D011809:Quinones; D013754:Tetracyclines; C018253:alpha-cyanocinnamate; D007073:Immunoglobulin E; D006923:Hymecromone; C009474:thioxolone; D005664:Furazolidone; D007216:Indoprofen; D010093:Oxolinic Acid