Dataset Information

Human IgE mAbs identify major antigens of parasitic worm infection.

ABSTRACT:

Background

Much of our understanding of the targets of IgE comes from studies of allergy, though little is known about the natural immunogenic targets seen after parasitic worm infections.

Objective

We used human monoclonal antibodies (mAbs) for an unbiased and comprehensive characterization of the immunodominant antigens targeted by IgE in conditions like allergy or helminth infection that are associated with elevated levels of IgE.

Methods

Using human hybridoma technology to immortalize IgE encoding B-cells from peripheral blood of subjects with filarial infections and elevated IgE, we generated naturally occurring human IgE mAbs. B-cell cultures were screened in an unbiased manner for IgE production without regard to specificity. Isolated IgE mAbs were then tested for binding to Brugia malayi somatic extracts using ImmunoCAP, immunoblot, and ELISA. Immunoprecipitation followed by mass spectrometry proteomics was used to identify helminth antigens that were then expressed in Escherichia coli for IgE binding characterization.

Results

We isolated 56 discrete IgE mAbs from 7 individuals with filarial infections. From these mAbs, we were able to definitively identify 19 filarial antigens. All IgE mAbs targeted filarial excreted/secretory proteins, including a family of previously uncharacterized proteins. Interestingly, the transthyretin-related antigens acted as the dominant inducer of the filaria-specific IgE antibody response. These filaria-specific IgE mAbs were potent inducers of anaphylaxis when passively administered to human FcεRI-expressing mice.

Conclusions

We generated human hybridomas secreting naturally occurring helminth-specific IgE mAbs from filarial-infected subjects. This work provides much-needed insight into the ontogeny of helminth-induced immune response and IgE antibody response.

SUBMITTER: Hadadianpour A

PROVIDER: S-EPMC9742163 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Human IgE mAbs identify major antigens of parasitic worm infection.

Hadadianpour Azadeh A Daniel Jacob J Zhang Jian J Spiller Benjamin W BW Makaraviciute Asta A DeWitt Åsa M ÅM Walden Heather S HS Hamilton Robert G RG Peebles R Stokes RS Nutman Thomas B TB Smith Scott A SA

The Journal of allergy and clinical immunology 20220624 6

<h4>Background</h4>Much of our understanding of the targets of IgE comes from studies of allergy, though little is known about the natural immunogenic targets seen after parasitic worm infections.<h4>Objective</h4>We used human monoclonal antibodies (mAbs) for an unbiased and comprehensive characterization of the immunodominant antigens targeted by IgE in conditions like allergy or helminth infection that are associated with elevated levels of IgE.<h4>Methods</h4>Using human hybridoma technology ...[more]

PMID: 35760390

Similar Datasets

Project description:The IgE response has been associated with both allergic reactions and immunity to metazoan parasites. Recently, we hypothesized that all environmental allergens bear structural homology to IgE-binding antigens from metazoan parasites and that this homology defines the relatively small number of protein families containing allergenic targets. In this study, known allergen structures (Pfam domains) from major environmental allergen families were used to predict allergen-like (SmProfilin, SmVAL-6, SmLipocalin, SmHSP20, Sm triosephosphate isomerase, SmThioredoxin, Sm superoxide dismutase, SmCyclophilin, and Sm phosphoglycerate kinase) and non-allergen-like [Sm dynein light chain (SmDLC), SmAldolase SmAK, SmUbiquitin, and Sm14-3-3] proteins in Schistosoma mansoni. Recombinant antigens were produced in Escherichia coli and IgG1, IgG4, and IgE responses against them measured in a cohort of people (n = 222) infected with S. mansoni. All allergen-like antigens were targeted by IgE responses in infected subjects, whilst IgE responses to the non-allergen-like antigens, SmAK, SmUbiquitin, and Sm14-3-3 were essentially absent being of both low prevalence and magnitude. Two new IgE-binding Pfam domain families, not previously described in allergen family databases, were also found, with prevalent IgE responses against SmDLC (PF01221) and SmAldolase (PF00274). Finally, it was demonstrated that immunoregulatory serological processes typically associated with allergens also occurred in responses to allergen-like proteins in S. mansoni infections, including the production of IgG4 in people responding with IgE and the down-regulation of IgE in response to increased antigen exposure from S. mansoni eggs. This study establishes that structures of known allergens can be used to predict IgE responses against homologous parasite allergen-like molecules (parallergens) and that serological responses with IgE/IgG4 to parallergens mirror those seen against allergens, supporting our hypothesis that allergenicity is rooted in expression of certain protein domain families in metazoan parasites.

Dataset Information

Human IgE mAbs identify major antigens of parasitic worm infection.

Background

Objective

Methods

Results

Conclusions

Publications

Human IgE mAbs identify major antigens of parasitic worm infection.

Similar Datasets

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