Abstract
Allergic reactions can be considered as maladaptive IgE immune responses towards environmental antigens. Intriguingly, these mechanisms are observed to be very similar to those implicated in the acquisition of an important degree of immunity against metazoan parasites (helminths and arthropods) in mammalian hosts. Based on the hypothesis that IgE-mediated immune responses evolved in mammals to provide extra protection against metazoan parasites rather than to cause allergy, we predict that the environmental allergens will share key properties with the metazoan parasite antigens that are specifically targeted by IgE in infected human populations. We seek to test this prediction by examining if significant similarity exists between molecular features of allergens and helminth proteins that induce an IgE response in the human host. By employing various computational approaches, 2712 unique protein molecules that are known IgE antigens were searched against a dataset of proteins from helminths and parasitic arthropods, resulting in a comprehensive list of 2445 parasite proteins that show significant similarity through sequence and structure with allergenic proteins. Nearly half of these parasite proteins from 31 species fall within the 10 most abundant allergenic protein domain families (EF-hand, Tropomyosin, CAP, Profilin, Lipocalin, Trypsin-like serine protease, Cupin, BetV1, Expansin and Prolamin). We identified epitopic-like regions in 206 parasite proteins and present the first example of a plant protein (BetV1) that is the commonest allergen in pollen in a worm, and confirming it as the target of IgE in schistosomiasis infected humans. The identification of significant similarity, inclusive of the epitopic regions, between allergens and helminth proteins against which IgE is an observed marker of protective immunity explains the ‘off-target’ effects of the IgE-mediated immune system in allergy. All these findings can impact the discovery and design of molecules used in immunotherapy of allergic conditions.
Highlights
Allergy is a hypersensitive immune reaction to environmental antigens from diverse sources such as foods, plants and innocuous organisms
We have established molecular similarity between parasite proteins and allergens that affect the nature of immune response and are able to predict the regions of parasite proteins that potentially share similarity with the IgE-binding region(s) of the allergens
Two main datasets were generated: Dataset 1 (Allergenic proteins, IgE/IgG4-binding peptides). (a) 2712 unique full-length protein sequences from various sources that are known to cause allergy and/or bind IgE were collated from the Allergome database [19]; (b) 2577 specific fragments from 190 proteins that are known to bind IgE and IgG4 antibodies in immunological assays were retrieved from the Immune Epitope Database (IEDB) database [36]
Summary
Allergy is a hypersensitive immune reaction to environmental antigens from diverse sources such as foods, plants and innocuous organisms. The mechanism responsible for eliciting the allergic reaction involves components of the immune system, in particular the IgE antibody isotype, which mediate the immune response against helminthic infection. IgE cross reactivity has been well established between some allergenic proteins and certain metazoan parasite proteins [15,16,17,18]. These immunological assays further suggest that are similar immune system components involved in acquiring immunity against helminths and in allergic conditions, but that the molecular targets for these responses may share key characteristics
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