Isoforms of Atopic Allergens with Reduced Allergenicity but Conserved T Cell Antigenicity: Possible Use for Specific Immunotherapy

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BACKGROUND: We analyzed the T cell activation potency and the IgE-binding properties (allergenicity) of nine isoforms of Bet v 1, the major allergen of birch pollen. METHODS: The capacity of recombinant Bet v 1 isoforms to bind serum IgE from allergic patients was evaluated by immunoblot experiments and skin prick tests. The potency of Bet v 1 isoallergens to activate T lymphocytes from birch-pollen-allergic patients was assayed using allergen-specific T cell clones. RESULTS: According to their ability to bind IgE from allergic patients in immunoblot experiments, Bet v 1 isoforms can be grouped into high-IgE-binding molecules and molecules with low/no IgE-binding activity. Representatively, isoform d was used in skin tests. Skin prick tests revealed no potency of this isoform to induce wheal and flare reactions in the skin of birch-pollen-allergic individuals. In contrast, isoform a and natural Bet v 1 displayed high allergenicity in vivo. On the other hand, Bet v 1 isoform d (low allergenicity) displayed significant higher T cell activation potency when compared to isoform a (high allergenicity). CONCLUSION: Based on these findings, we propose a new form of specific immunotherapy using hypoallergenic recombinant allergen isoforms.

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