Expression of a human IgG4 antibody, BAB2, with specificity for the major Birch pollen allergen, Bet v 1 in Escherichia coli: recombinant BAB2 Fabs enhance the allergic reaction.
BACKGROUND
Antigen recognition by antibodies of different isotypes can result in completely different effects as exemplified by Type I allergy. While the IgE-antibody-mediated release of biological mediators constitutes the immunopathological basis for the immediate symptoms observed in allergic patients, allergen-specific IgG antibodies are thought to have protective effects.


METHODS
Cell lines secreting five human monoclonal IgG antibodies (BAB1-BAB5) with specificity for the major birch pollen allergen Bet v 1 were established from a birch-pollen-allergic patient who had received birch- pollen-specific immunotherapy. The influence of the Bet v 1-specific IgG antibodies on IgE binding to Bet v 1 was investigated. BAB2 was expressed in Escherichia coli as recombinant Fab, purified and tested for its ability to modulate Bet v 1-induced immediate-type skin reactions.


RESULTS
The BAB antibodies belonged to different IgG subclasses (BAB1: IgG1; BAB2, BAB3, BAB5: IgG4; and BAB4: IgG2) reflecting a tendency towards Th2. BAB1 represented the only antibody which strongly blocked IgE binding to Bet v 1, whereas BAB 3-BAB5 had little effect on IgE binding. Surprisingly, natural BAB2 antibodies as well as recombinant BAB2 Fabs strongly enhanced IgE binding to Bet v 1 and Bet v 1-induced immediate-type skin reactions and thus represent 'enhancing antibodies'.


CONCLUSIONS
The demonstration that anti-allergen IgG antibodies can also enhance IgE binding to a given allergen explains the unpredictability of specific immunotherapy as well as the controversy on the role of IgG in atopy.
Eibensteiner
P
P
Institute of General and Experimental Pathology, AKH, Univerity of Vienna, Austria.
Denépoux
S
S
Steinberger
P
P
Kraft
D
D
Visco
V
V
Banchereau
J
J
Lebecque
S
S
Valenta
R
R
D000485:Allergens / Q000276:immunology*; D000918:Antibody Specificity; D052179:Antigens, Plant; D000939:Epitopes; D004926:Escherichia coli; D005803:Genes, Immunoglobulin; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D010940:Plant Proteins / Q000276:immunology*; D011058:Pollen; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D010940:Plant Proteins; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula