Comparisons of allergenic and metazoan parasite proteins: allergy the price of immunity

Tyagi, Nidhi, Farnell, Edward J., Fitzsimmons, Colin M., Ryan, Stephanie, Tukahebwa, Edridah, Maizels, Rick M., Dunne, David W., Thornton, Janet M., and Furnham, Nicholas (2015) Comparisons of allergenic and metazoan parasite proteins: allergy the price of immunity. PLoS Computational Biology, 11 (10). e1004546. pp. 1-24.

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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.

Item ID: 41491
Item Type: Article (Research - C1)
ISSN: 1553-7358
Additional Information:

© 2015 Tyagi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funders: Wellcome Trust (WT), European Commission (EC), Medical Research Council (MRC)
Projects and Grants: WT 094317MA , WT 083931/Z/07/Z , WT 094317/Z/10/Z, EC FP7-CP-IP-SICA scheme grant 242107, WT 094317, WT 090281, MRC MR/K020420/1
Date Deposited: 02 Dec 2015 02:09
FoR Codes: 06 BIOLOGICAL SCIENCES > 0603 Evolutionary Biology > 060307 Host-Parasite Interactions @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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