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

Antia, R., Tyagi, N., Farnell, E. J., Fitzsimmons, C. M., Ryan, S., Tukahebwa, E., Maizels, R. M. , Dunne, D. W., Thornton, J. M. and Furnham, N. (2015) Comparisons of allergenic and metazoan parasite proteins: allergy the price of immunity. PLoS Computational Biology, 11(10), e1004546. (doi: 10.1371/journal.pcbi.1004546) (PMID:26513360) (PMCID:PMC4626114)

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 Type: Articles
• Additional Information: Funding: This work was funded by Wellcome Trust (http://www.wellcome.ac.uk/) grant WT094317MA to NT, Wellcome Trust (http://www.wellcome.ac.uk/) programme grant WT 083931/Z/07/Z to DWD, Wellcome Trust (http://www.wellcome.ac.uk/) WT 094317/Z/10/Z and European Commission (http://ec.europa.eu/index_en.htm) FP7-CP-IP-SICA scheme grant 242107 to EF and CF, Wellcome Trust grant 094317 to DWD, RMM and JT and 090281 to SR and MRC (http://www.mrc.ac.uk), funding MR/K020420/1 to NF.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maizels, Professor Rick
• Authors: Antia, R., Tyagi, N., Farnell, E. J., Fitzsimmons, C. M., Ryan, S., Tukahebwa, E., Maizels, R. M., Dunne, D. W., Thornton, J. M., and Furnham, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Computational Biology
• Publisher: Public Library of Science
• ISSN: 1553-734X
• ISSN (Online): 1553-7358
• Copyright Holders: Copyright © 2015 Tyagi et al.
• First Published: First published in PLoS Computational Biology
• Publisher Policy: Reproduced under a Creative Commons license