Cross‐protection of AIT‐induced antibodies to related allergens requires a high degree of structural identity

Abstract

BackgroundIn contrast to sublingual immunotherapy (SLIT) with recombinant Mal d 1 (rMal d 1‐SLIT), SLIT with rBet v 1 (rBet v 1‐SLIT) induced Mal d 1‐cross‐reactive antibodies without IgE‐blocking activity. To elucidate whether the development of cross‐protective IgG responses depends on the degree of molecular identity of allergens we compared the cross‐reactivity, cross‐blocking activity, and affinity of SLIT‐induced antibodies with allergens of varying amino acid sequence identities to Bet v 1 and Mal d 1, namely Cor a 1.04 (hazelnut), Pru av 1 (cherry), and Dau c 1 (carrot).MethodsAllergen‐specific antibodies were quantified by ELISA. IgE blocking was analyzed by inhibition of allergen‐induced basophil activation and IgE‐facilitated allergen‐presentation to T cells. The affinity of SLIT‐induced antibodies was studied by acidic dissociation ELISA and competition ELISA. Identical surface areas on allergens were predicted using an in‐house designed script based on structural alignments.ResultsrBet v 1‐SLIT‐induced IgG antibodies cross‐reacted with all allergens except Dau c 1. rMal d 1‐SLIT‐induced antibodies predominantly cross‐reacted with Pru av 1 and displayed significantly higher IgE blocking to Pru av 1 than rBet v 1‐SLIT‐induced antibodies. rMal d 1‐SLIT‐induced IgG1 showed higher affinity to Mal d 1 and Pru av 1. Surface analysis revealed 84% identical area on Mal d 1 and Pru av 1. Furthermore, we identified two surface areas potentially containing epitopes present on these allergens and absent on Bet v 1.ConclusionIn summary, our findings suggest that a relatively high threshold of similarity is required to establish effective cross‐blocking antibodies to related allergens. Apparently, the structural identity between Bet v 1 and Mal d 1 is below this threshold. Therefore, this study may explain why immunotherapy with birch pollen allergen often fails to reduce birch pollen‐related apple allergy.