title: Protease recognition sites in Bet v 1a are cryptic, explaining its slow processing relevant to its allergenicity.
abstract: Despite a high similarity with homologous protein families, only few proteins trigger an allergic immune response with characteristic TH2 polarization. This puzzling observation is illustrated by the major birch pollen allergen Bet v 1a and its hypoallergenic protein isoforms, e.g., Bet v 1d. Given the key role of proteolytic processing in antigen presentation and T cell polarization, we investigated the recognition of Bet v 1 isoforms by the relevant protease cathepsin S. We found that at moderately acidic pH values Bet v 1a bound to cathepsin S with significantly lower affinity and was more slowly cleaved than its hypoallergenic isoform Bet v 1d. Only at pH values ≤ 4.5 the known proteolytic cleavage sites in Bet v 1a became accessible, resulting in a strong increase in affinity towards cathepsin S. Antigen processing and class II MHC loading occurs at moderately acidic compartments where processing of Bet v 1a and Bet v 1d differs distinctly. This difference translates into low and high density class II MHC loading and subsequently in TH2 and TH1 polarization, respectively.
authors.affiliation: Department of Molecular Biology, University of Salzburg, Billrothstr. 11, A-5020 Salzburg, Austria.
authors.forename: Regina
authors.initials: R
authors.lastname: Freier
authors.affiliation: Department of Molecular Biology, University of Salzburg, Billrothstr. 11, A-5020 Salzburg, Austria.
authors.forename: Elfriede
authors.initials: E
authors.lastname: Dall
authors.affiliation: Department of Molecular Biology, University of Salzburg, Billrothstr. 11, A-5020 Salzburg, Austria.
authors.forename: Hans
authors.initials: H
authors.lastname: Brandstetter
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000595:Amino Acid Sequence; D052179:Antigens, Plant / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D029662:Betula / Q000276:immunology; D001665:Binding Sites; D002403:Cathepsins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011058:Pollen / Q000276:immunology; D016415:Sequence Alignment
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula; D002403:Cathepsins; C028217:cathepsin S