Crossreactivity and T‐cell epitope specificity of Bet v 1‐specific T cells suggest the involvement of multiple isoallergens in sensitization to birch pollen

Abstract
Summary: Background Allergen‐specific T lymphocytes play an important role in the pathophysiology of atopic disease. Detailed studies of their epitope‐specificity and crossreactivity are required for the development of novel approaches for specific immunotherapy.Objectives The aim of the study was to characterize the fine specificity of Bet v 1‐specific T cells from allergic donors.Methods Polyclonal T‐cell lines (TCL) and T‐cell clones (TCC), specific for Bet v 1, the major birch (Betula verrucosa) pollen allergen, were isolated from the peripheral blood of three birch‐allergic patients. Their epitope‐specificity was studied using overlapping synthetic peptides, and crossreactivity with other tree pollen allergens of the Fagales order was evaluated. In addition, the Bet v 1‐specific TCC were studied for their phenotype and cytokine production.Results All isolated Bet v 1‐specific TCC (19/21 CD4+, 2/21 CD8+) reacted with affinity purified Bet v 1, but showed different reactivities with recombinant Bet v 1 (rBet v 1), and with group 1 allergens from other Fagales species. Epitope mapping of rBet v 1‐reactive TCC with synthetic peptides of Bet v 1 showed the presence of four T‐cell epitopes. Polyclonal T‐cell lines reacted with 13 different peptides, and displayed even broader crossreactivity with group 1 pollen allergens from other Fagales members.Conclusion This study demonstrates that apart from T‐cell epitopes of rBet v 1, many other crossreactive or Bet v 1 isoallergen‐specific epitopes exist. This indicates that isoallergenic variation plays an important role in the induction of Bet v 1‐specific and crossreactive T‐cell responsiveness to allergens.

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