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IgE-mediated facilitated antigen presentation underlies higher immune responses in peanut allergy

Authors

  • V. Turcanu,

    1. Department of Paediatric Allergy, Division of Asthma, Allergy and Lung Biology, MRC & Asthma UK Centre in the Allergic Mechanisms of Asthma, King’s College London, London, UK
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  • A. C. Stephens,

    1. Department of Paediatric Allergy, Division of Asthma, Allergy and Lung Biology, MRC & Asthma UK Centre in the Allergic Mechanisms of Asthma, King’s College London, London, UK
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  • S. M. H. Chan,

    1. Department of Paediatric Allergy, Division of Asthma, Allergy and Lung Biology, MRC & Asthma UK Centre in the Allergic Mechanisms of Asthma, King’s College London, London, UK
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  • F. Rancé,

    1. Hôpital des Enfants Pneumologie-Allergologie, CHU de Toulouse, France
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  • G. Lack

    1. Department of Paediatric Allergy, Division of Asthma, Allergy and Lung Biology, MRC & Asthma UK Centre in the Allergic Mechanisms of Asthma, King’s College London, London, UK
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  • Edited by: Hans-Uwe Simon

Prof. Gideon Lack, King’s College London, Department of Paediatric Allergy, 2nd Floor, Evelina Children’s Hospital, Lambeth Palace Road, London SE1 7EH, UK.
Tel.: +44 207 188 9730
Fax: +44 207 928 4458
E-mail: gideon.lack@kcl.ac.uk

Abstract

To cite this article: Turcanu V, Stephens AC, Chan SMH, Rancé F, Lack G. IgE-mediated facilitated antigen presentation underlies higher immune responses in peanut allergy. Allergy 2010; 65: 1274–1281.

Abstract

Background:  Peanut allergy poses significant healthcare problems, because its prevalence is increasing in many countries, and it is rarely outgrown. To explore the immunological mechanisms that underlie peanut allergy and tolerance, we compared the peanut-specific responses of peanut-allergic (PA) and nonallergic (NA) individuals.

Methods:  We measured peanut-specific peripheral blood mononuclear cells (PBMC) proliferation using tritiated thymidine. The frequency of peanut-specific T cells amongst PBMC was determined by carboxyfluorescein succinimidyl ester labelling. The role of IgE-dependent facilitated antigen presentation (FAP) in modulating proliferation was investigated by depleting IgE from plasma with anti-IgE-coated beads and then assessing PBMC proliferation in the presence of IgE-depleted or nondepleted plasma.

Results:  We found that peanut-specific PBMC proliferation is higher and peaks earlier in PA than in NA donors. We investigated the immunological mechanisms that could underlie these differences. We found that both PA and NA have memory responses to peanut, but the frequency of peanut-specific T cells is higher in PA than in NA. Facilitated antigen presentation could cause both the higher proliferation and precursor frequency in PA. Facilitated antigen presentation activity in vitro was confirmed by showing that IgE depletion decreases proliferation, while adding IgE back restores it.

Conclusion:  Our results identify FAP as a mechanism that underlies higher responses to peanut in PA. In these individuals, high levels of peanut-specific IgE could furthermore maintain long-term allergic T-cell responses. We raise the question whether, in the future, therapies targeting IgE such as anti-IgE antibodies may be used to suppress these T-cell responses.

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