Reducing the solubility of the major birch pollen allergen Bet v 1 by particle-loading mitigates Th2 responses
Background: Solubility is a common feature of allergens. However, the causative relationship between this protein-intrinsic feature and sensitization capacity of allergens is not fully understood. This study aimed to proof the concept of solubility as a protein intrinsic feature of allergens. Method...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Allergology International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1323893024000819 |
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| author | Amin Kraiem Erica Pelamatti Sophie Grosse-Kathoefer Hilal Demir Ute Vollmann Caroline Ehgartner Maria Stigler Benjamin Punz Litty Johnson Nicola Hüsing Barbara Bohle Lorenz Aglas |
| author_facet | Amin Kraiem Erica Pelamatti Sophie Grosse-Kathoefer Hilal Demir Ute Vollmann Caroline Ehgartner Maria Stigler Benjamin Punz Litty Johnson Nicola Hüsing Barbara Bohle Lorenz Aglas |
| author_sort | Amin Kraiem |
| collection | DOAJ |
| description | Background: Solubility is a common feature of allergens. However, the causative relationship between this protein-intrinsic feature and sensitization capacity of allergens is not fully understood. This study aimed to proof the concept of solubility as a protein intrinsic feature of allergens. Methods: The soluble birch pollen allergen Bet v 1 was covalently coupled to 1 μm silica particles. IgE-binding and -cross-linking capacity was assessed by inhibition ELISA and mediator release assay, respectively. Alterations in adjuvanticity by particle-loading were investigated by activation of dendritic cells, mast cells and the Toll-like receptor 4 pathway as well as by Th2 polarization in an IL-4 reporter mouse model. In BALB/c mice, particle-loaded and soluble Bet v 1 were compared in a model of allergic sensitization. Antigen uptake and presentation was analysed by restimulating human Bet v 1-specific T cell lines. Results: Covalent coupling of Bet v 1 to silica particles resulted in an insoluble antigen with retained IgE-binding and -cross-linking capacity and no increase in adjuvanticity. In vivo, particle-loaded Bet v 1 induced significantly lower Bet v 1-specific (s)IgE, whereas sIgG1 and sIgG2a levels remained unaffected. The ratio of Th2 to Th1 cells was significantly lower in mice sensitized with particle-loaded Bet v 1. Particle-loading of Bet v 1 resulted in a 24-fold higher T cell activation capacity in Bet v 1-specific T cell lines, indicating more efficient uptake and presentation than of soluble Bet v 1. Conclusions: Our results show that solubility is a decisive factor contributing to the sensitization capacity of allergens. The reduction in sensitization capacity of insoluble, particle-loaded antigens results from enhanced antigen uptake and presentation compared to soluble allergens. |
| format | Article |
| id | doaj-art-7da7ef8fcd5b49bbbbf6e150713a966f |
| institution | Kabale University |
| issn | 1323-8930 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Allergology International |
| spelling | doaj-art-7da7ef8fcd5b49bbbbf6e150713a966f2025-01-04T04:56:05ZengElsevierAllergology International1323-89302025-01-01741126135Reducing the solubility of the major birch pollen allergen Bet v 1 by particle-loading mitigates Th2 responsesAmin Kraiem0Erica Pelamatti1Sophie Grosse-Kathoefer2Hilal Demir3Ute Vollmann4Caroline Ehgartner5Maria Stigler6Benjamin Punz7Litty Johnson8Nicola Hüsing9Barbara Bohle10Lorenz Aglas11Department of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaInstitute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, AustriaInstitute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, AustriaDepartment of Chemistry and Physics of Materials, University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaDepartment of Chemistry and Physics of Materials, University of Salzburg, Salzburg, AustriaInstitute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, Austria; Corresponding author. Department of Biosciences and Medical Biology, University of Salzburg, Hellbrunner Str. 34, A-5020 Salzburg, Austria.Background: Solubility is a common feature of allergens. However, the causative relationship between this protein-intrinsic feature and sensitization capacity of allergens is not fully understood. This study aimed to proof the concept of solubility as a protein intrinsic feature of allergens. Methods: The soluble birch pollen allergen Bet v 1 was covalently coupled to 1 μm silica particles. IgE-binding and -cross-linking capacity was assessed by inhibition ELISA and mediator release assay, respectively. Alterations in adjuvanticity by particle-loading were investigated by activation of dendritic cells, mast cells and the Toll-like receptor 4 pathway as well as by Th2 polarization in an IL-4 reporter mouse model. In BALB/c mice, particle-loaded and soluble Bet v 1 were compared in a model of allergic sensitization. Antigen uptake and presentation was analysed by restimulating human Bet v 1-specific T cell lines. Results: Covalent coupling of Bet v 1 to silica particles resulted in an insoluble antigen with retained IgE-binding and -cross-linking capacity and no increase in adjuvanticity. In vivo, particle-loaded Bet v 1 induced significantly lower Bet v 1-specific (s)IgE, whereas sIgG1 and sIgG2a levels remained unaffected. The ratio of Th2 to Th1 cells was significantly lower in mice sensitized with particle-loaded Bet v 1. Particle-loading of Bet v 1 resulted in a 24-fold higher T cell activation capacity in Bet v 1-specific T cell lines, indicating more efficient uptake and presentation than of soluble Bet v 1. Conclusions: Our results show that solubility is a decisive factor contributing to the sensitization capacity of allergens. The reduction in sensitization capacity of insoluble, particle-loaded antigens results from enhanced antigen uptake and presentation compared to soluble allergens.http://www.sciencedirect.com/science/article/pii/S1323893024000819Allergic sensitizationBet v 1IgESilica particlesSolubility |
| spellingShingle | Amin Kraiem Erica Pelamatti Sophie Grosse-Kathoefer Hilal Demir Ute Vollmann Caroline Ehgartner Maria Stigler Benjamin Punz Litty Johnson Nicola Hüsing Barbara Bohle Lorenz Aglas Reducing the solubility of the major birch pollen allergen Bet v 1 by particle-loading mitigates Th2 responses Allergology International Allergic sensitization Bet v 1 IgE Silica particles Solubility |
| title | Reducing the solubility of the major birch pollen allergen Bet v 1 by particle-loading mitigates Th2 responses |
| title_full | Reducing the solubility of the major birch pollen allergen Bet v 1 by particle-loading mitigates Th2 responses |
| title_fullStr | Reducing the solubility of the major birch pollen allergen Bet v 1 by particle-loading mitigates Th2 responses |
| title_full_unstemmed | Reducing the solubility of the major birch pollen allergen Bet v 1 by particle-loading mitigates Th2 responses |
| title_short | Reducing the solubility of the major birch pollen allergen Bet v 1 by particle-loading mitigates Th2 responses |
| title_sort | reducing the solubility of the major birch pollen allergen bet v 1 by particle loading mitigates th2 responses |
| topic | Allergic sensitization Bet v 1 IgE Silica particles Solubility |
| url | http://www.sciencedirect.com/science/article/pii/S1323893024000819 |
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