Responses of human birch pollen allergen-reactive T cells to chemically modified allergens (allergoids)

Background Allergoids are widely used in specific immunotherapy for the tre atment of IgE-mediated allergic diseases. Objective The aim of this study was to analyse whether a modification of bi rch pollen allergens with formaldehyde affects the availability of T-cell e pitopes. Methods Efficient modification of the allergens was verified by determining IgE and IgG binding activity using ELISA inhibition tests. T-cell response s to birch pollen allergoids were analysed in polyclonal systems, using per ipheral blood mononuclear cells (PBMC) of five birch pollen-allergic indivi duals, as well as birch pollen extract-reactive T-cell lines (TCL), establi shed from the peripheral blood of 14 birch pollen-allergic donors. To deter mine whether the modification of natural (n)Bet v 1 with formaldehyde or ma leic anhydride results in epitope-specific changes in T-cell reactivities, 22 Bet v 1-specific T-cell clones (TCC), established from nine additional b irch pollen-allergic individuals, were tested for their reactivity with the se products. Results The majority of PBMC and TCL showed a reduced response to the birch pollen extract allergoid. Bet v 1-specific TCC could be divided into aller goid-reactive and -non-reactive TCC. No simple correlation between possible modification sites of formaldehyde in the respective T-cell epitopes and t he stimulatory potential of the allergoid was observed. Mechanisms of suppr ession or of anergy induction were excluded as an explanation for the non-r eactivity of representative TCC. All TCC could be stimulated by maleylated and unmodified nBet v I to a similar extent. Conclusion These results demonstrate differences in the availability of T-c ell epitopes between allergoids and unmodified allergens, which are most li kely due to structural changes within the allergen molecule.