Recombinant allergen molecules: tools to study effector cell activation.
The IgE antibody-mediated activation of allergic effector cells is the key pathomechanism underlying the immediate symptoms of Type I allergy, a genetically determined hypersensitivity disease affecting 25% of the population. In recent years important environmental allergens and their epitopes have become available as structurally defined recombinant molecules. In addition, corresponding human monoclonal IgE and IgG antibodies have been isolated. This review summarizes data obtained regarding the three-dimensional structure of allergens, their IgE epitopes and the recognition of allergens by IgE and IgG antibodies. In particular, we discuss results of recent in vitro and in vivo studies with defined allergen molecules, their epitopes and the corresponding antibodies which support the hypothesis that the density and geometrical arrangement of IgE epitopes on a particular allergen molecule may profoundly affect effector cell activation. If the structural requirements for effector cell activation can be delineated, it may be envisaged that, based on this knowledge, allergens can be converted into hypoallergenic immunogens by reorientation of IgE epitopes. Such allergen derivatives may be used for allergen-specific immunotherapy with reduced risk of inducing anaphylactic side effects.
Valenta
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R
Department of Pathophysiology, Vienna General Hospital, University of Vienna, Austria. Rudolf.Valenta@akh-wien.ac.at
Kraft
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D000485:Allergens / Q000009:adverse effects / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001491:Basophils / Q000378:metabolism*; D003285:Contractile Proteins; D003888:Desensitization, Immunologic; D000939:Epitopes / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D008840:Microfilament Proteins / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology; D008958:Models, Molecular; D008970:Molecular Weight; D011058:Pollen / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology; D051304:Profilins; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use / Q000633:toxicity
D000485:Allergens; D000911:Antibodies, Monoclonal; D003285:Contractile Proteins; D000939:Epitopes; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D008840:Microfilament Proteins; D051304:Profilins; D011994:Recombinant Proteins; D007073:Immunoglobulin E