CROSS-REACTIVITY AND T-CELL EPITOPE SPECIFICITY OF BET-V-1-SPECIFIC T-CELLS SUGGEST THE INVOLVEMENT OF MULTIPLE ISOALLERGENS IN SENSITIZATION TO BIRCH POLLEN

Background Allergen-specific T lymphocytes play an important role in t he pathophysiology of atopic disease. Detailed studies of their epitop e-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 ver rucosa) pollen allergen, were isolated from the peripheral blood of th ree birch-allergic patients. Their epitope-specificity was studied usi ng 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 pr oduction. Results All isolated Bet v 1-specific TCC (19/21 CD4(+), 2/2 1 CD8(+)) reacted with affinity purified Bet v 1, but showed different reactivities with recombinant Bet v 1 (rBet v 1), and with group 1 al lergens from other Fagales species. Epitope mapping of rBet v 1-reacti ve TCC with synthetic peptides of Bet v 1 showed the presence of four T-cell epitopes. Polyclonal T-cell lines reacted with 13 different pep tides, and displayed even broader crossreactivity with group 1 pollen allergens from other Fagales members. Conclusion This study demonstrat es that apart from T-cell epitopes of rBet v 1, many other crossreacti ve or Bet v 1 isoallergen-specific epitopes exist. This indicates that isoallergenic variation plays an important role in the induction of B et v 1-specific and crossreactive T-cell responsiveness to allergens.