| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* ALK-Abelló, Research Department, Hørsholm, Denmark; and
Structural Biology Group, Department of Medicinal Chemistry, Danish University of Pharmaceutical Sciences, Copenhagen, Denmark
Specific allergy vaccination is an efficient treatment for allergic disease; however, the development of safer vaccines would enable a more general use of the treatment. Determination of molecular structures of allergens and allergen-Ab complexes facilitates epitope mapping and enables a rational approach to the engineering of allergen molecules with reduced IgE binding. In this study, we describe the identification and modification of a human IgE-binding epitope based on the crystal structure of Bet v 1 in complex with the BV16 Fab' fragment. The epitope occupies 
10% of the molecular surface area of Bet v 1 and is clearly conformational. A synthetic peptide representing a sequential motif in the epitope (11 of 16 residues) did not inhibit the binding of mAb BV16 to Bet v 1, illustrating limitations in the use of peptides for B cell epitope characterization. The single amino acid substitution, Glu45-Ser, was introduced in the epitope and completely abolished the binding of mAb BV16 to the Bet v 1 mutant within a concentration range 1000-fold higher than wild type. The mutant also showed up to 50% reduction in the binding of human polyclonal IgE, demonstrating that glutamic acid 45 is a critical amino acid also in a major human IgE-binding epitope. By solving the three-dimensional crystal structure of the Bet v 1 Glu45-Ser mutant, it was shown that the change in immunochemical activity is directly related to the Glu45-Ser substitution and not to long-range structural alterations or collapse of the Bet v 1 mutant tertiary structure.
This article has been cited by other articles:
|
|
 |
|
  M. Li, A. Gustchina, J. Alexandratos, A. Wlodawer, S. Wunschmann, C. L. Kepley, M. D. Chapman, and A. Pomes Crystal Structure of a Dimerized Cockroach Allergen Bla g 2 Complexed with a Monoclonal Antibody J. Biol. Chem., August 15, 2008; 283(33): 22806 - 22814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gafvelin, S. Parmley, T. Neimert-Andersson, U. Blank, T. L. J. Eriksson, M. van Hage, and J. Punnonen Hypoallergens for Allergen-specific Immunotherapy by Directed Molecular Evolution of Mite Group 2 Allergens J. Biol. Chem., February 9, 2007; 282(6): 3778 - 3787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Chan, S. T. Ong, S. Y. Ong, F. T. Chew, and Y. K. Mok Nuclear magnetic resonance structure-based epitope mapping and modulation of dust mite group 13 allergen as a hypoallergen. J. Immunol., April 15, 2006; 176(8): 4852 - 4860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Scholl, N. Kalkura, Y. Shedziankova, A. Bergmann, P. Verdino, R. Knittelfelder, T. Kopp, B. Hantusch, C. Betzel, K. Dierks, et al. Dimerization of the Major Birch Pollen Allergen Bet v 1 Is Important for its In Vivo IgE-Cross-Linking Potential in Mice J. Immunol., November 15, 2005; 175(10): 6645 - 6650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Holm, M. Gajhede, M. Ferreras, A. Henriksen, H. Ipsen, J. N. Larsen, L. Lund, H. Jacobi, A. Millner, P. A. Wurtzen, et al. Allergy Vaccine Engineering: Epitope Modulation of Recombinant Bet v 1 Reduces IgE Binding but Retains Protein Folding Pattern for Induction of Protective Blocking-Antibody Responses J. Immunol., October 15, 2004; 173(8): 5258 - 5267. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
