Academic Journal
Patient-Derived IgG Epitope Mapping of Bet v 1 Reveals Hypoallergenic Peptide Candidates for Safe and Next-Generation Allergen Immunotherapy.
| Τίτλος: | Patient-Derived IgG Epitope Mapping of Bet v 1 Reveals Hypoallergenic Peptide Candidates for Safe and Next-Generation Allergen Immunotherapy. |
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| Συγγραφείς: | Šošić L; Department of Dermatology, University of Zurich, Schlieren, Switzerland., Paolucci M; Department of Dermatology, University of Zurich, Schlieren, Switzerland., Streuli A; Laboratory for Functional Immune Repertoire Analysis, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.; Laboratory for Pharmaceutical Analytics, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland., Melillo DA; Department of Dermatology, University of Zurich, Schlieren, Switzerland., Jiang T; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Campana R; Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Lang CCV; Department of Dermatology, University of Zurich, Schlieren, Switzerland.; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland., Kündig TM; Department of Dermatology, University of Zurich, Schlieren, Switzerland.; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland., Steuer C; Laboratory for Pharmaceutical Analytics, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland., Eyer K; Laboratory for Functional Immune Repertoire Analysis, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Johansen P; Department of Dermatology, University of Zurich, Schlieren, Switzerland.; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. |
| Πηγή: | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Clin Exp Allergy] 2026 Aug; Vol. 56 (8), pp. 881-892. Date of Electronic Publication: 2026 Mar 10. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 8906443 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2222 (Electronic) Linking ISSN: 09547894 NLM ISO Abbreviation: Clin Exp Allergy Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford : Blackwell Scientific Publications, c1989- |
| Ιατρικοί όροι (MeSH): | Immunoglobulin G*/immunology , Immunoglobulin G*/blood , Desensitization, Immunologic*/methods , Antigens, Plant*/immunology , Antigens, Plant*/chemistry , Allergens*/immunology , Peptides*/immunology , Rhinitis, Allergic, Seasonal*/immunology , Rhinitis, Allergic, Seasonal*/therapy , Epitope Mapping*, Basophils/immunology ; Immunoglobulin E/immunology ; Immunoglobulin E/blood ; Epitopes/immunology ; Humans ; Female ; Adult ; Male |
| Περίληψη: | Background: Allergen immunotherapy (AIT) is the only curative treatment for allergic diseases, primarily by inducing allergen-neutralising IgG antibodies. However, its use is limited by frequent allergic adverse events. Objective: To facilitate the design of IgG-epitope-based peptide vaccines, this study aimed to identify IgG-binding regions on the major birch pollen allergen, Bet v 1, using patient-derived immune profiles. Methods: Blood samples were collected from 30 birch pollen-allergic patients, both AIT-treated and untreated; healthy individuals were included as controls. Sera were analysed for allergen-specific IgE, IgG, and IgG4, and basophil degranulation inhibition was assessed in humanised RBL cells and blood from allergic individuals. We used DropMap microfluidics for single-cell affinity profiling of IgG- and IgG4-secreting B cells. IgG epitopes were mapped using overlapping peptides and CLIPS technology. Candidate AIT peptides were synthesised on solid phase via Fmoc strategy, and their allergenicity was assessed in basophil degranulation and cellular antigen stimulation assays. Results: Sera from AIT-treated patients exhibited elevated IgG and IgG4 levels and enhanced inhibition of basophil degranulation. Single-cell analysis indicated IgG-affinity maturation with AIT. IgG-epitope mapping identified four distinct, non-overlapping IgG-binding regions on Bet v 1. Six peptides derived from these regions were successfully produced and did not induce basophil degranulation in vitro. The application of DropMap microfluidics allowed high-resolution single B-cell analysis, providing novel insights into allergen-specific B-cell responses and the effects of AIT at the clonal level. Conclusion: This integrated approach identifies hypoallergenic peptides that selectively engage protective IgG responses and offers a framework for developing safer, next-generation immunotherapies for allergic disease. (© 2026 The Author(s). Clinical & Experimental Allergy published by John Wiley & Sons Ltd.) |
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| Grant Information: | 25866.2 PFLS-LS Innosuisse - Schweizerische Agentur für Innovationsförderung; 407940_206399 Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung; STEB-2022-002 Foundation for Research in Science and the Humanities at the University of Zurich |
| Contributed Indexing: | Keywords: DropMap; allergen immunotherapy; antibodies; basophil activation assay; epitope mapping; synthetic peptides |
| Substance Nomenclature: | 0 (Immunoglobulin G) 0 (Antigens, Plant) 0 (Allergens) 0 (Peptides) 126161-14-6 (Bet v 1 allergen, Betula) 37341-29-0 (Immunoglobulin E) 0 (Epitopes) |
| Entry Date(s): | Date Created: 20260310 Date Completed: 20260802 Latest Revision: 20260813 |
| Update Code: | 20260813 |
| PubMed Central ID: | PMC13429318 |
| DOI: | 10.1111/cea.70276 |
| PMID: | 41806123 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1365-2222 |
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| DOI: | 10.1111/cea.70276 |