Bet v 1‐independent sensitization to major allergens in Fagales pollen: Evidence at the T‐cell level. Issue 3 (8th December 2022) - Polak, Dominika
Abstract: Background: In birch‐dominated areas, allergies to pollen from trees of the order Fagales are considered to be initiated by the major birch pollen allergen Bet v 1. However, the sensitizing activity of Bet v 1‐homologs in Fagales pollen might be underestimated. Allergen‐specific T‐cells are crucial in the sensitization process. The T‐cell response to major allergens from alder, hazel, oak, hornbeam, chestnut, beech, and chestnut pollen has not yet been analyzed. Here, we characterized the cellular cross‐reactivity of major allergens in Fagales pollen with Bet v 1. Methods: T‐cell‐lines (TCL) were established from allergic individuals with Aln g 1, Car b 1, Ost c 1, Cor a 1, Fag s 1, Cas s 1, and Que a 1, and tested for reactivity with Bet v 1 and synthetic overlapping 12‐mer peptides representing its primary sequence. Aln g 1‐specific TCL was additionally tested with Aln g 1‐derived peptides and all allergens. IgE‐competition experiments with Aln g 1 and Bet v 1 were performed. Results: T‐cell‐lines initiated with Fagales pollen allergens varied strongly in their reactivity with Bet v 1 and by the majority responded stronger to the original stimulus. Cross‐reactivity was mostly restricted to the epitope Bet v 1142–153 . No distinct cross‐reactivity of Aln g 1‐specific T‐cells with Bet v 1 was detected. Among 22 T‐cell epitopes, Aln g 1 contained two immunodominant epitopes. Bet v 1 inhibited IgE‐binding to Aln g 1 less potently than Aln g 1 itself. Conclusion: The cellular cross‐reactivity of major Fagales pollen allergens with Bet v 1 was unincisive, particularly for Aln g 1, most akin to Bet v 1. Our results indicate that humoral and cellular responses to these allergens are not predominantly based on cross‐reactivity with the major birch pollen allergen but suggest a Bet v 1‐independent sensitization in individuals from birch tree‐dominated areas. Abstract : In birch‐dominated areas, Bet v 1 is considered as primary sensitizer of IgE‐mediated allergies to pollen from birch‐related trees. T‐cell lines established with Bet v 1‐homologous pollen allergens show limited cross‐reactivity with Bet v 1. Despite high amino acid sequence homology of major Fagales allergens with Bet v 1 T‐cell cross‐reactivity is restricted to very few epitopes of the major birch pollen allergen. Two dominant T‐cell epitopes of Aln g 1 indicate genuine sensitizing capacity.Abbreviation: TCL, T cell line.