Allergen mimotopes for 3-dimensional epitope search and induction of antibodies inhibiting human IgE

被引:55
作者
Ganglberger, E [1 ]
Grünberger, K [1 ]
Sponer, B [1 ]
Radauer, C [1 ]
Breiteneder, H [1 ]
Boltz-Nitulescu, G [1 ]
Scheiner, O [1 ]
Jensen-Jarolim, E [1 ]
机构
[1] Univ Vienna, Sch Med, AKH, Dept Pathophysiol, A-1090 Vienna, Austria
关键词
Bet v 1; IgE epitope; mimotope; phage; biopanning; blocking IgG;
D O I
10.1096/fj.99-1000com
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, S-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 Angstrom 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.
引用
收藏
页码:2177 / 2184
页数:8
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