Distinct epitope structures of defensin-like proteins linked to proline-rich regions give rise to differences in their allergenic activity

I. Pablos, S. Eichhorn, Y. Machado, P. Briza, A. Neunkirchner, B. Jahn-Schmid, S. Wildner, W. T. Soh, C. Ebner, J. W. Park, W. F. Pickl, N. Arora, S. Vieths, F. Ferreira, G. Gadermaier

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Background: Art v 1, Amb a 4, and Par h 1 are allergenic defensin-polyproline–linked proteins present in mugwort, ragweed, and feverfew pollen, respectively. We aimed to investigate the physicochemical and immunological features underlying the different allergenic capacities of those allergens. Methods: Recombinant defensin-polyproline–linked proteins were expressed in E. coli and physicochemically characterized in detail regarding identity, secondary structure, and aggregation status. Allergenic activity was assessed by mediator releases assay, serum IgE reactivity, and IgE inhibition ELISA using sera of patients from Austria, Canada, and Korea. Endolysosomal protein degradation and T-cell cross-reactivity were studied in vitro. Results: Despite variations in the proline-rich region, similar secondary structure elements were observed in the defensin-like domains. Seventy-four percent and 52% of the Austrian and Canadian patients reacted to all three allergens, while Korean patients were almost exclusively sensitized to Art v 1. This was reflected by IgE inhibition assays demonstrating high cross-reactivity for Austrian, medium for Canadian, and low for Korean sera. In a subgroup of patients, IgE reactivity toward structurally altered Amb a 4 and Par h 1 was not changed suggesting involvement of linear epitopes. Immunologically relevant endolysosomal stability of the defensin-like domain was limited to Art v 1 and no T-cell cross-reactivity with Art v 1 25-36 was observed. Conclusions: Despite structural similarity, different IgE-binding profiles and proteolytic processing impacted the allergenic capacity of defensin-polyproline–linked molecules. Based on the fact that Amb a 4 demonstrated distinct IgE-binding epitopes, we suggest inclusion in molecule-based allergy diagnosis.

Original languageEnglish
Pages (from-to)431-441
Number of pages11
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume73
Issue number2
DOIs
Publication statusPublished - 2018 Feb 1

Bibliographical note

Funding Information:
Dr. Pablos Ocampo reports grants from Austrian Research Fund, during the conduct of the study; Dr. Eichhorn reports grants from Austrian Science Fund, during the conduct of the study; Dr. Machado reports grants from Austrian Science Fund, during the conduct of the study; Dr. Neunkirchner reports grants from Austrian Science Fund, during the conduct of the study; Dr. Jahn-Schmid reports grants from Austrian Science Fund, grants from Austrian National Bank, during the conduct of the study; Dr. Wildner reports grants from Christian Doppler Research Association, during the conduct of the study; Dr. Pickl reports grants from Austrian Science Foundation (FWF), during the conduct of the study; and he holds stocks of Bio-may AG, Vienna, Austria and received honoraria from Novartis for expert advise and seminars/talks; Dr. Arora reports grants from Department of Biotechnology, Government of India., during the conduct of the study; Prof. Vieths reports personal fees from Arzte-€ verband Deutscher Allergologen, personal fees from Swiss Society for Allergy and Immunology, personal fees from Schattauer Aller-gologie Handbuch, personal fees from Elsevier Nahrungsmittelal-lergien und Intoleranzen, personal fees from Karger Food Allergy: Molecular Basis and Clinical Practice, non-financial support from German Research Foundation, non-financial support from European Directorate for the Quality of Medicines and Health Care, nonfinancial support from European Academy of Allergy and Clinical Immunology, non-financial support from German Chemical Society (GDCh), non-financial support from AKM Allergiekongress, nonfinancial support from International Union of Immunological Societies, personal fees from University Hospital Gießen / Marburg, personal fees from University of Bonn, personal fees from Pharmacon, personal fees from Medical University of Vienna, Austria, personal fees from Gesellschaft fu€r p€adiatrische Allergologie und Umweltmedizin, non-financial support from World Allergy Organization, non-financial support from Technical University of Munich, non-financial support from Austrian Society for Dermatology and Venerology, outside the submitted work; Dr. Gadermaier reports grants from Austrian Science Fund, during the conduct of the study; personal fees from Thermo Fisher Scientific, outside the submitted work. The other authors declare that they have no relevant conflict of interests.

Funding Information:
W1213, Molecular, Cellular and Clinical Allergology, Grant/Award Number: MCCA, W1248, SFB project F4609, P20011; Austrian National Bank, Grant/Award Number: Anniversary Fund 13800; Austrian National Foundation of Research, Technology and Development; Austrian Federal Ministry of Science, Research and Economy; Land Salzburg; INDIGO DBT2-038 GENALL, Grant/Award Number: 01DQ13003; German Federal Ministry of Education and Research; Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) by Ministry of Health & Welfare, Grant/Award Number: HI14C1324; Department of Biotechnology, India, Grant/ Award Number: BT/IN/New Indigo/01/NA/ 2013

Funding Information:
We are grateful to Alain Didierlaurent for providing serum samples. The study was funded by the ERA New INDIGO project I 1152, Molecular Biotechnology for Allergy Diagnosis and Therapy (GEN-ALL), the Doctoral program “Immunity in Cancer and Allergy,” W1213, and “Molecular, Cellular and Clinical Allergology,” MCCA, W1248, and the SFB project F4609 of the Austrian Science Fund (FWF); The Austrian Federal Ministry of Science, Research and Economy and the National Foundation of Research, Technology and Development, and Land Salzburg; INDIGO DBT2-038 GENALL No. 01DQ13003, German Federal Ministry of Education and Research; and Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) by the Ministry of Health & Welfare (grant number: HI14C1324). The funding sources had no role in study design, data analysis, and interpretation, writing or article submission.

Publisher Copyright:
© 2017 The Authors Allergy Published by John Wiley / Sons Ltd.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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