title: 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.
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.
authors.affiliation: Department of Pathophysiology, Centre for Physiology, Pathophysiology and Immunology Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Smole
authors.forename: Nina
authors.initials: N
authors.lastname: Balazs
authors.forename: Karin
authors.initials: K
authors.lastname: Hoffmann-Sommergruber
authors.forename: Christian
authors.initials: C
authors.lastname: Radauer
authors.forename: Christine
authors.initials: C
authors.lastname: Hafner
authors.forename: Michael
authors.initials: M
authors.lastname: Wallner
authors.forename: Fatima
authors.initials: F
authors.lastname: Ferreira
authors.forename: Roland
authors.initials: R
authors.lastname: Grössinger
authors.forename: Esther C
authors.initials: EC
authors.lastname: de Jong
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagner
authors.forename: Heimo
authors.initials: H
authors.lastname: Breiteneder
mesh_terms: D000485:Allergens / Q000276:immunology*; D052179:Antigens, Plant / Q000276:immunology*; D029662:Betula / Q000276:immunology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D010940:Plant Proteins / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D020033:Protein Isoforms / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D018793:Interleukin-13; D015848:Interleukin-5; D010940:Plant Proteins; D020033:Protein Isoforms; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E