Complementation of Der P 2-induced histamine release from human basophils sensitized with monoclonal IgE: not only by IgE, but also by IgG antibodies directed to a nonoverlapping epitope of Der p 2.
The interaction of free allergen with two (or more) IgE molecules bound to the high-affinity receptor for IgE (FcepsilonRI) on mast cells and basophilic granulocytes results in the release of inflammatory mediators. The role of allergen-specific IgG antibodies in the allergic reaction in human beings is less clear. We produced two chimeric IgE antibodies, hIgE-Dp2A and hIgE-Dp2B, directed to two nonoverlapping epitopes (A and B) of the house dust mite allergen Der p 2. Chimeric IgG1 and IgG4 variants of these antibodies were produced also. Basophil activation by the house dust mite allergen Der p 2 was induced after sensitization of basophils with a mixture of chimeric hIgE-Dp2A and hIgE-Dp2B antibodies but not after sensitization by the individual IgE antibodies alone. Basophil activation was also shown after sensitization with hIgE-Dp2A and stimulation with Der p 2 incubated with hIgG1-Dp2B or hIgG4-Dp2B antibodies. Both IgE and IgG antibodies directed to the other nonoverlapping epitope complemented the sensitization by the hIgE-Dp2A antibody. Nonsensitized basophils were not activated by the Der p 2/hIgG-Dp2 mixtures. These results indicate that allergen-specific IgG can complement an IgE-dependent reaction and therefore under certain conditions can act as an anaphylactic antibody.
Schuurman
J
J
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam.
Perdok
G J
GJ
Mueller
G A
GA
Aalberse
R C
RC
D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D039741:Antigens, Dermatophagoides; D001491:Basophils / Q000276:immunology*; D003001:Cloning, Molecular; D000939:Epitopes / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D051379:Mice; D016254:Mutagenesis, Insertional; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D039741:Antigens, Dermatophagoides; D000939:Epitopes; D006023:Glycoproteins; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E