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Protease recognition sites in Bet v 1a are cryptic, explaining its slow processing relevant to its allergenicity

Despite a high similarity with homologous protein families, only few proteins trigger an allergic immune response with characteristic T(H)2 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. Give...

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Detalles Bibliográficos
Autores principales: Freier, Regina, Dall, Elfriede, Brandstetter, Hans
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522599/
https://www.ncbi.nlm.nih.gov/pubmed/26235974
http://dx.doi.org/10.1038/srep12707
Descripción
Sumario:Despite a high similarity with homologous protein families, only few proteins trigger an allergic immune response with characteristic T(H)2 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 T(H)2 and T(H)1 polarization, respectively.