IgE mimotopes of birch pollen allergen Bet v 1 induce blocking IgG in mice.
BACKGROUND
The induction of nonanaphylactogenic 'blocking' IgG antibodies capable of inhibiting the IgE/allergen interaction represents a favorable therapeutic concept for type I allergy. However, IgG antibodies to allergens may block or enhance specific IgE binding, depending on the recognized epitope. Taking the major birch pollen allergen Bet v 1 as a model, we developed a strategy for the precise induction of IgG antibodies of a desired epitope specificity.


METHODS
Random phage display peptide libraries were applied to define peptide structures mimicking natural epitopes (mimotopes) of Bet v 1. Selections were performed with BIP 1, a murine monoclonal antibody known to enhance the IgE binding to Bet v 1, and with anti-Bet v 1 IgE purified from patients' sera. The characterized Bet v 1 mimotopes were used to localize the corresponding epitope at the surface of Bet v 1 by a computer-aided mathematical approach based on the three-dimensional structure and the chemical character of the amino acids. The Bet v 1 mimotopes were further used to immunize BALB/c mice. The specificity of the induced antibodies was tested by immunoblotting and inhibition assays.


RESULTS
With the three-dimensional epitope search it became possible to localize a discontinuous IgE epitope on the surface of Bet v 1 in a substantial distance from the IgG epitope of the monoclonal antibody BIP 1. Moreover, we could demonstrate that phage displaying mimotopes are immunogenic vectors for the precise induction of epitope-specific IgG. Immunization with BIP 1 mimotopes induced IgG enhancing the IgE binding to Bet v 1, whereas immunization with IgE mimotopes resulted in IgG capable of blocking human IgE binding in vitro.


CONCLUSIONS
Allergen mimotopes can be used for the induction of anti allergen IgG of desired specificity. We propose that mimotope immunotherapy based on IgE mimotopes generated by biopannings may represent a future concept for therapy of type I allergy.
Ganglberger
E
E
Department of Pathophysiology (formally Department of General and Experimental Pathology), University of Vienna, Austria.
Grünberger
K
K
Wiedermann
U
U
Vermes
M
M
Sponer
B
B
Breiteneder
H
H
Scheiner
O
O
Boltz
G
G
Jensen-Jarolim
E
E
D000485:Allergens; D000818:Animals; D000918:Antibody Specificity; D052179:Antigens, Plant; D000939:Epitopes / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D018716:Molecular Mimicry; D019151:Peptide Library; D010940:Plant Proteins / Q000276:immunology*; D011058:Pollen / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; D000939:Epitopes; D007074:Immunoglobulin G; D019151:Peptide Library; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E