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Comparisons of Allergenic and Metazoan Parasite Proteins: Allergy the Price of Immunity.

Tyagi N, Farnell EJ, Fitzsimmons CM, Ryan S, Tukahebwa E, Maizels RM, Dunne DW, Thornton JM, Furnham N - PLoS Comput. Biol. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: The EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus

Pfam domain families that are highly populated with allergenic protein sequences.Protein domain families considered for this analysis are highlighted in the box based on the families presented in the article co-authored by Fitzsimmons and Dunne [21].
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pcbi.1004546.g004: Pfam domain families that are highly populated with allergenic protein sequences.Protein domain families considered for this analysis are highlighted in the box based on the families presented in the article co-authored by Fitzsimmons and Dunne [21].

Mentions: The 2712 unique UniProt protein sequence entries corresponding to protein molecules listed in the Allergome database are distributed in 331 Pfam protein domain families. Protein domain families with allergenic entries are relatively few and account for merely 2.2% of total 14831 protein domain families specified in Pfam database (Fig 3). There are 128 protein families that are comprised of only one allergenic protein member. A total of 1389 out of 2712 allergenic molecules (~51%) are members of just 20 protein domain families (Fig 4). Among these families, Tropomyosin (Pfam accession: PF00261) constitutes 217 allergenic molecules (~8% of all allergens).


Comparisons of Allergenic and Metazoan Parasite Proteins: Allergy the Price of Immunity.

Tyagi N, Farnell EJ, Fitzsimmons CM, Ryan S, Tukahebwa E, Maizels RM, Dunne DW, Thornton JM, Furnham N - PLoS Comput. Biol. (2015)

Pfam domain families that are highly populated with allergenic protein sequences.Protein domain families considered for this analysis are highlighted in the box based on the families presented in the article co-authored by Fitzsimmons and Dunne [21].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4626114&req=5

pcbi.1004546.g004: Pfam domain families that are highly populated with allergenic protein sequences.Protein domain families considered for this analysis are highlighted in the box based on the families presented in the article co-authored by Fitzsimmons and Dunne [21].
Mentions: The 2712 unique UniProt protein sequence entries corresponding to protein molecules listed in the Allergome database are distributed in 331 Pfam protein domain families. Protein domain families with allergenic entries are relatively few and account for merely 2.2% of total 14831 protein domain families specified in Pfam database (Fig 3). There are 128 protein families that are comprised of only one allergenic protein member. A total of 1389 out of 2712 allergenic molecules (~51%) are members of just 20 protein domain families (Fig 4). Among these families, Tropomyosin (Pfam accession: PF00261) constitutes 217 allergenic molecules (~8% of all allergens).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: The EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus