Molecular characterization of human IgG monoclonal antibodies specific for the major birch pollen allergen Bet v 1. Anti-allergen IgG can enhance the anaphylactic reaction.
We report the molecular characterization of five human monoclonal antibodies, BAB1-5 (BAB1: IgG(1); BAB4: IgG(2); BAB2, 3, 5: IgG(4)), with specificity for the major birch pollen allergen, Bet v 1. BAB1-5 were obtained after immunotherapy and contained a high degree of somatic mutations indicative of an antigen-driven affinity maturation process. While BAB1 inhibited the binding of patients IgE to Bet v 1, BAB2 increased IgE recognition of Bet v 1, and, even as Escherichia coli-expressed Fab, augmented Bet v 1-induced immediate type skin reactions. The demonstration that IgG antibodies can enhance allergen-induced allergic reactions is likely to explain the unpredictability of specific immunotherapy.
Denépoux
S
S
Laboratory for Immunological Research, Schering-Plough, Dardilly, France.
Eibensteiner
P B
PB
Steinberger
P
P
Vrtala
S
S
Visco
V
V
Weyer
A
A
Kraft
D
D
Banchereau
J
J
Valenta
R
R
Lebecque
S
S
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D000918:Antibody Specificity; D052179:Antigens, Plant; D000939:Epitopes / Q000276:immunology; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000628:therapy; D007073:Immunoglobulin E / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000276:immunology; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry / Q000276:immunology*; D011058:Pollen / Q000276:immunology*
D000485:Allergens; D000911:Antibodies, Monoclonal; D052179:Antigens, Plant; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E