Dataset Information

Ara h 1-reactive T cells in individuals with peanut allergy.

ABSTRACT:

Background

Effective immunotherapy for peanut allergy is hampered by a lack of understanding of peanut-reactive CD4(+) T cells.

Objective

To identify, characterize, and track Ara h 1-reactive cells in subjects with peanut allergy by using Ara h 1-specific class II tetramers.

Methods

Tetramer-guided epitope mapping was used to identify the antigenic peptides within the peanut allergen Ara h 1. Subsequently, HLA class II/Ara h 1-specific tetramers were used to determine the frequency and phenotype of Ara h 1-reactive T cells in subjects with peanut allergy. Cytokine profiles of Ara h 1-reactive T cells were also determined.

Results

Multiple Ara h 1 epitopes with defined HLA restriction were identified. Ara h 1-specific CD4(+) T cells were detected in all of the subjects with peanut allergy tested. Ara h 1-reactive T cells in subjects with allergy expressed CCR4 but did not express CRTH2. The percentage of Ara h1-reactive cells that expressed the ?7 integrin was low compared with total CD4(+) T cells. Ara h 1- reactive cells that secreted IFN-?, IL-4, IL-5, IL-10, and IL-17 were detected.

Conclusion

In individuals with peanut allergy, Ara h 1-reactive T cells occurred at moderate frequencies, were predominantly CCR4(+) memory cells, and produced IL-4. Class II tetramers can be readily used to detect Ara h 1-reactive T cells in the peripheral blood of subjects with peanut allergy without in vitro expansion and would be effective for tracking peanut-reactive CD4(+) T cells during immunotherapy.

SUBMITTER: DeLong JH

PROVIDER: S-EPMC3130623 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ara h 1-reactive T cells in individuals with peanut allergy.

DeLong Jonathan H JH Simpson Kelly Hetherington KH Wambre Erik E James Eddie A EA Robinson David D Kwok William W WW

The Journal of allergy and clinical immunology 20110402 5

<h4>Background</h4>Effective immunotherapy for peanut allergy is hampered by a lack of understanding of peanut-reactive CD4(+) T cells.<h4>Objective</h4>To identify, characterize, and track Ara h 1-reactive cells in subjects with peanut allergy by using Ara h 1-specific class II tetramers.<h4>Methods</h4>Tetramer-guided epitope mapping was used to identify the antigenic peptides within the peanut allergen Ara h 1. Subsequently, HLA class II/Ara h 1-specific tetramers were used to determine the f ...[more]

PMID: 21459424

Similar Datasets

Project description:IntroductionAs the only market-authorized allergen immunotherapy (AIT) for peanut allergy is accompanied by a high risk of side effects and mainly induces robust desensitization without sustained efficacy, novel treatment options are required. Peanut-specific plant-derived eBioparticles (eBPs) surface expressing Ara h 2 at high density have been shown to be very hypoallergenic. Here, we assessed the dendritic cell (DC)-activating and T cell polarization capacity of these peanut-specific eBPs.MethodsRoute and kinetics of eBP uptake were studied by (imaging) flow cytometry using monocyte-derived DCs incubated with fluorescently-labelled Ara h 2 eBPs or natural Ara h 2 (nAra h 2) in the presence or absence of inhibitors that block pathways involved in macropinocytosis, phagocytosis, and/or receptor-mediated uptake. DC activation was monitored by flow cytometry (maturation marker expression) and ELISA (cytokine production). T cell polarization was assessed by co-culturing DCs exposed to Ara h 2 eBPs or nAra h 2 with naïve CD4+ T cells, followed by flow cytometry assessment of intracellular IFNγ+ (Th1) and IL-13+ (Th2), and CD25+CD127-Foxp3+ regulatory T cells (Tregs). The suppressive activity of Tregs was tested using a suppressor assay.ResultsAra h 2 eBPs were taken up by DCs through actin-dependent pathways. They activated DCs demonstrated by an induced expression of CD83 and CD86, and production of TNFα, IL-6, and IL-10. eBP-treated DCs polarized naïve CD4+ T cells towards Th1 cells, while reducing Th2 cell development. Furthermore, eBP-treated DCs induced reduced the frequency of Foxp3+ Tregs but did not significantly affect T cell IL-10 production or T cells with suppressive capacity. In contrast, DC activation and Th1 cell polarization were not observed for nAra h 2.ConclusionAra h 2 eBPs activate DCs that subsequently promote Th1 cell polarization and reduce Th2 cell polarization. These characteristics mark Ara h 2 eBPs as a promising novel candidate for peanut AIT.

Dataset Information

Ara h 1-reactive T cells in individuals with peanut allergy.

Background

Objective

Methods

Results

Conclusion

Publications

Ara h 1-reactive T cells in individuals with peanut allergy.

Similar Datasets

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