Allergen mimotopes for 3-dimensional epitope search and induction of antibodies inhibiting human IgE.
There is no definite information available on the structural characteristics of IgE binding epitopes on allergenic molecules, although it is widely accepted that most of them are conformational. In the current study we aimed to characterize the IgE epitope of Bet v 1, the major birch pollen allergen, by the application of phage display peptide libraries. We purified IgE specific for Bet v 1 from allergic patients' sera to select mimotopes representing artificial IgE epitopes by biopanning of phage libraries. By linear alignment, it was not possible to attribute mimotope sequences to the primary structure of Bet v 1. We developed a computer-aided, 3-dimensional coarse-grained epitope search. The 3-dimensional search, followed by statistical analysis, revealed an exposed area on the Bet v 1 molecule (located between residues 9-22 and 104-123) as the IgE binding structure. The IgE epitope was located at a 30 A distance from a previously described IgG epitope and the respective mimotope, designated Bet mim E. Such mimotopes could potentially be used for the induction of IgG capable of interfering with the IgE/allergen interaction. To test this hypothesis, we immunized BALB/c mice with the phage-displayed Bet mim E. Immunizations resulted in the induction of Bet v 1-specific IgG, which was able to block the IgE binding to Bet v 1 in vitro. Based on these observations, we propose that immunotherapy with IgE mimotopes generated by biopannings result in formation of blocking IgG. We conclude that mimotope immunotherapy may represent a new and promising concept for treatment of type I allergic disease.
Ganglberger
E
E
Department of Pathophysiology, AKH, Medical School, University of Vienna, A-1090 Vienna, Austria.
Grunberger
K
K
Sponer
B
B
Radauer
C
C
Breiteneder
H
H
Boltz-Nitulescu
G
G
Scheiner
O
O
Jensen-Jarolim
E
E
D000485:Allergens; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D000918:Antibody Specificity; D052179:Antigens, Plant; D001666:Binding Sites, Antibody / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011487:Protein Conformation
D000485:Allergens; D000911:Antibodies, Monoclonal; D052179:Antigens, Plant; D000939:Epitopes; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E