Abstract
BackgroundDue to high IgE recognition frequency and high allergenic activity, Der p 5 and Der p 21 are clinically important house dust mite (HDM) allergens. The objective of this study was to characterize the immunodominant IgE epitopes of Der p 5 and Der p 21 responsible for their high allergenic activity.MethodsA panel of 12 overlapping peptides spanning the Der p 5 and Der p 21 sequence were synthesized to search for sequential IgE epitopes by direct testing for allergic patients' IgE reactivity. Peptide‐specific antibodies raised in rabbits were used in inhibition studies for localizing conformational IgE epitopes which were visualized on the surfaces of the allergen structures by molecular modelling. IgE cross‐reactivity between the allergens was investigated by IgE inhibition studies.ResultsImmunodominant IgE epitopes defined by allergic patients' IgE on Der p 5 and Der p 21 were primarily of the conformational, discontinuous type including N‐ and C‐terminal portions of the protein. They could be located on each allergen on one area with similar localization, but despite similar structure of the allergens, no relevant IgE cross‐reactivity could be detected.ConclusionOur study shows that Der p 5 and Der p 21 contain a major conformational IgE epitope‐containing area located on similar portions of their structure, but they lack relevant IgE cross‐reactivity. These data are important for the development of modern allergy vaccines based on defined molecules for allergen‐specific immunotherapy of HDM allergy.
Highlights
A recently published study investigating the prevalence of IgE recognition and the development of the evolution of IgE sensitizations to house dust mite (HDM) allergens in a large birth cohort in Germany highlighted the importance of Der p 5 and Der p 21 because approximately 20% to 30% of the participants were sensitized against these allergens.[13]
In another study performed in HDM-allergic children suffering only from rhinitis or rhinitis and asthma, sensitization to Der p 5 and Der p 21 occurred more frequently in the children who suffered from asthma and asthmatic children more frequently recognized several different HDM allergens including Der p 5 and Der p 21 compared to children without asthma.[14]
It is difficult to develop HDM allergy vaccines based on natural allergen extracts which protect HDM-allergic patients who are sensitized to these allergens
Summary
House dust mites (HDMs) belong to the most potent and frequent allergen sources worldwide with a prevalence of sensitization of more than 40% within atopic populations.[1,2] House dust mite - sensitized patients suffer from a variety of allergic symptoms, in particular from respiratory and skin allergy, and often exhibit severe respiratory symptoms such as asthma.[3,4] HDM is a complex allergen source with more than 20 different reported allergen groups, only certain allergens are of high clinical relevance, among. HDM is a complex allergen source with more than 20 different reported allergen groups, only certain allergens are of high clinical relevance, among. It is difficult to develop HDM allergy vaccines based on natural allergen extracts which protect HDM-allergic patients who are sensitized to these allergens. Several new forms of allergy vaccines have been successfully evaluated in clinical trials which are based on defined molecular components.[17,18] The construction of these vaccines depends heavily on the definition of the clinically relevant allergens of a given allergen source and the knowledge of IgE and T-cell epitopes of the key allergens. Der p 21 seems to have a similar three-dimensional structure (ie, forms a three-helical bundle protein) but shows no IgE cross-reactivity with Der p 5.10 Here, we performed a detailed analysis of the IgE epitopes of Der p 5 and Der p 21 to break the ground for a broadly protective HDM allergy vaccine
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