1QMR

BIRCH POLLEN ALLERGEN BET V 1 MUTANT N28T, K32Q, E45S, P108G

Summary for 1QMR

• Entry DOI: 10.2210/pdb1qmr/pdb
• Related: 1B6F 1BTV 1BV1
• Descriptor: MAJOR POLLEN ALLERGEN BET V 1-A (2 entities in total)
• Functional Keywords: allergen, pathogenesis-related protein
• Biological source: BETULA VERRUCOSA (WHITE BIRCH)
• Total number of polymer chains: 1
• Total formula weight: 17331.43

Authors

Henriksen, A.,Holm, J.O.,Spangfort, M.D.,Gajhede, M. (deposition date: 1999-10-06, release date: 2000-10-12, Last modification date: 2023-12-13)

Primary citation

Holm, J.,Gajhede, M.,Ferreras, M.,Henriksen, A.,Ipsen, H.,Larsen, J.N.,Lund, L.,Jacobi, H.,Millner, A.,Wurtzen, P.A.,Spangfort, M.D.
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., 173:5258-5267, 2004

PubMed Abstract: Human type 1 immediate allergic response symptoms are caused by mediator release from basophils and mast cells. This event is triggered by allergens aggregating preformed IgE Abs bound to the high-affinity receptor (FcepsilonRI) on these cells. Thus, the allergen/IgE interaction is crucial for the cascade leading to the allergic and anaphylactic response. Two genetically engineered forms of the white birch pollen major allergen Bet v 1 with point mutations directed at molecular surfaces have been characterized. Four and nine point mutations led to a significant reduction of the binding to human serum IgE, suggesting a mutation-induced distortion of IgE-binding B cell epitopes. In addition, the mutated allergens showed a decrease in anaphylactic potential, because histamine release from human basophils was significantly reduced. Retained alpha-carbon backbone folding pattern of the mutated allergens was indicated by x-ray diffraction analysis and circular dichroism spectroscopy. The rBet v 1 mutants were able to induce proliferation of T cell lines derived from birch pollen allergic patients. The stimulation indices were similar to the indices of nonmutated rBet v 1 and natural Bet v 1 purified from birch pollen. The ability of anti-rBet v 1 mutant specific mouse IgG serum to block binding of human serum IgE to rBet v 1 demonstrates that the engineered rBet v 1 mutants are able to induce Abs reactive with nonmodified Bet v 1. rBet v 1 mutants may constitute vaccine candidates with improved efficacy/safety profiles for safer allergy vaccination.

PubMed: 15470071
DOI: 10.4049/jimmunol.173.8.5258

Experimental method

X-RAY DIFFRACTION (2.15 Å)