| Autor: |
Kitzmüller, C., Wallner, M., Deifl, S., Mutschlechner, S., Walterskirchen, C., Zlabinger, G. J., Ferreira, F., Bohle, B. |
| Předmět: |
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| Zdroj: |
Allergy; Nov2012, Vol. 67 Issue 11, p1375-1382, 8p, 1 Chart, 5 Graphs |
| Abstrakt: |
Background BM4 is a novel genetically engineered variant of the major birch pollen allergen Bet v 1 that lacks the typical Bet v 1-like fold and displays negligible Ig E-binding but strong T cell-activating capacity. The aim of this study was to elucidate possible differences between BM4 and Bet v 1 in internalization, antigen processing, and presentation. Methods Proliferative responses to BM4 and Bet v 1 of peripheral blood mononuclear cells and Bet v 1-specific T-cell clones were compared. Fluorescently labeled BM4 and Bet v 1 were used to study surface binding, endocytosis, and intracellular degradation by monocyte-derived DC (md DC). Both proteins were digested by endolysosomal extracts of md DC. BM4- and Bet v 1-pulsed md DC were employed to assess the kinetics of activation of Bet v 1-specific T-cell clones and the polarization of naïve T cells. Results BM4 displayed a significantly stronger T cell-activating capacity than Bet v 1. Furthermore, BM4 showed increased surface binding and internalization as well as faster endolysosomal degradation compared with Bet v 1. BM4-pulsed md DC induced enhanced proliferative responses at earlier time-points in Bet v 1-specific T-cell clones and promoted less IL-5 production in T cells than Bet v 1-pulsed md DC. Conclusion The loss of the Bet v 1-fold changes the protein's interaction with the human immune system at the level of antigen-presenting cells resulting in altered T-cell responses. By combining low Ig E-binding with strong and modulating T cell-activating capacity, BM4 represents a highly interesting candidate for specific immunotherapy of birch pollen allergy. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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