Differential T-cell responses and allergen uptake after exposure of dendritic cells to the birch pollen allergens Bet v 1.0101, Bet v 1.0401 and Bet v 1.1001

• Published in: Immunobiology (1979) Vol. 215; no. 11; pp. 903 - 909
• Main Authors: Smole, Ursula, Balazs, Nina, Hoffmann-Sommergruber, Karin, Radauer, Christian, Hafner, Christine, Wallner, Michael, Ferreira, Fatima, Grössinger, Roland, de Jong, Esther C, Wagner, Stefan, Breiteneder, Heimo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01-11-2010
• Subjects: Advanced Basic Science; Allergen uptake; Allergens - immunology; Allergy; Allergy and Immunology; Antigens, Plant - immunology; Bet v 1.0101; Bet v 1.0401; Bet v 1.1001; Betula - immunology; Coculture Techniques; Dendritic cells; Dendritic Cells - immunology; Humans; Immunoglobulin E - immunology; Interleukin-13 - biosynthesis; Interleukin-5 - biosynthesis; Plant Proteins - immunology; Pollen - immunology; Protein Isoforms - immunology; T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism; Fluorescein isothiocyanate; Allergy; Dendritic cell; Dendritic cells; T cells; Bet v 1.0401; Bet v 1.0101; FITC; MDDC; Allergen uptake; Maturation factors; MF; Monocyte-derived dendritic cell; Bet v 1.1001; DC
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2009.11.003

Abstract The major birch pollen allergen Bet v 1 is present in pollen as a mixture of at least 14 isoforms that share high sequence and structural identities. These isoforms possess either a high or a low IgE-binding capacity which defines them as allergenic or hypoallergenic. Recently, we could demonstrate that only the allergenic isoform Bet v 1.0101 was able to induce an IgE response in birch pollen allergic individuals. The hypoallergenic isoforms Bet v 1.0401 and Bet v 1.1001 were unable to induce IgE synthesis. T-helper cell responses against allergens are characterised by increased levels of Th2 cytokines. Therefore, we examined extent and polarisation of the Th cell response and the kinetics of the allergen uptake after exposure of dendritic cells (DCs) to these isoforms. Monocyte-derived DCs (MDDCs) from birch pollen allergic and non-atopic individuals stimulated with Bet v 1.0101, Bet v 1.0401 or Bet v 1.1001 in combination with the maturation factors TNF-α and IL-1β resulted in a mature DC phenotype as measured by costimulatory molecule up-regulation. Only Bet v 1.0101-stimulated MDDCs from allergic subjects enhanced proliferation of autologous Th cells and the expression of the Th2 cytokines IL-5 and IL-13. Immature MDDCs of allergic individuals internalised equivalent amounts of the allergenic Bet v 1.0101 and the hypoallergenic Bet v 1.0401. In contrast, the uptake of the hypoallergenic Bet v 1.0401 by immature MDDCs of non-atopic individuals was significantly higher. These results provide evidence that DCs discriminate between allergens and highly related hypoallergens. This process may have an impact on the early phase of sensitisation.