TY  - JOUR
A1  - Berkner, Hanna
A1  - Seutter von Loetzen, Christian
A1  - Hartl, Maximilian
A1  - Randow, Stefanie
A1  - Gubesch, Michaela
A1  - Vogel, Lothar
A1  - Husslik, Felix
A1  - Reuter, Andreas
A1  - Lidholm, Jonas
A1  - Ballmer-Weber, Barbara
A1  - Vieths, Stefan
A1  - Rösch, Paul
A1  - Schiller, Dirk
T1  - Enlarging the toolbox for allergen epitope definition with an allergen-type model protein
T2  - PLoS One
N2  - Background: Birch pollen-allergic subjects produce polyclonal cross-reactive IgE antibodies that mediate pollen-associated food allergies. The major allergen Bet v 1 and its homologs in plant foods bind IgE in their native protein conformation. Information on location, number and clinical relevance of IgE epitopes is limited. We addressed the use of an allergen-related protein model to identify amino acids critical for IgE binding of PR-10 allergens.
Method: Norcoclaurine synthase (NCS) from meadow rue is structurally homologous to Bet v 1 but does not bind Bet v 1-reactive IgE. NCS was used as the template for epitope grafting. NCS variants were tested with sera from 70 birch pollen allergic subjects and with monoclonal antibody BV16 reported to compete with IgE binding to Bet v 1.
Results: We generated an NCS variant (Δ29NCSN57/I58E/D60N/V63P/D68K) harboring an IgE epitope of Bet v 1. Bet v 1-type protein folding of the NCS variant was evaluated by 1H-15N-HSQC NMR spectroscopy. BV16 bound the NCS variant and 71% (50/70 sera) of our study population showed significant IgE binding. We observed IgE and BV16 cross-reactivity to the epitope presented by the NCS variant in a subgroup of Bet v 1-related allergens. Moreover BV16 blocked IgE binding to the NCS variant. Antibody cross-reactivity depended on a defined orientation of amino acids within the Bet v 1-type conformation.
Conclusion: Our system allows the evaluation of patient-specific epitope profiles and will facilitate both the identification of clinically relevant epitopes as biomarkers and the monitoring of therapeutic outcomes to improve diagnosis, prognosis, and therapy of allergies caused by PR-10 proteins.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/35361
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-353619
SN  - 1932-6203
N1  - Copyright: © 2014 Berkner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 9
IS  - (10):e111691
PB  - PLoS
CY  - Lawrence, Kan.
ER  -