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Reducing the solubility of the major birch pollen allergen Bet v 1 by particle-loading mitigates Th2 responses.
Kraiem, Amin; Pelamatti, Erica; Grosse-Kathoefer, Sophie; Demir, Hilal; Vollmann, Ute; Ehgartner, Caroline; Stigler, Maria; Punz, Benjamin; Johnson, Litty; Hüsing, Nicola; Bohle, Barbara; Aglas, Lorenz.
Afiliación
  • Kraiem A; Department of Biosciences and Medical Biology, University of Salzburg, Salzburg, Austria.
  • Pelamatti E; Department of Biosciences and Medical Biology, University of Salzburg, Salzburg, Austria.
  • Grosse-Kathoefer S; Department of Biosciences and Medical Biology, University of Salzburg, Salzburg, Austria.
  • Demir H; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
  • Vollmann U; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
  • Ehgartner C; Department of Chemistry and Physics of Materials, University of Salzburg, Salzburg, Austria.
  • Stigler M; Department of Biosciences and Medical Biology, University of Salzburg, Salzburg, Austria.
  • Punz B; Department of Biosciences and Medical Biology, University of Salzburg, Salzburg, Austria.
  • Johnson L; Department of Biosciences and Medical Biology, University of Salzburg, Salzburg, Austria.
  • Hüsing N; Department of Chemistry and Physics of Materials, University of Salzburg, Salzburg, Austria.
  • Bohle B; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
  • Aglas L; Department of Biosciences and Medical Biology, University of Salzburg, Salzburg, Austria. Electronic address: lorenz.aglas@plus.ac.at.
Allergol Int ; 2024 Aug 17.
Article en En | MEDLINE | ID: mdl-39155214
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Allergol Int Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Allergol Int Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido