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Facilitated antigen presentation and its inhibition by blocking IgG antibodies depends on IgE repertoire complexity - 11/08/11

Doi : 10.1016/j.jaci.2011.01.062 
Jens Holm, PhD , Nicholas Willumsen, MSc, Peter A. Würtzen, PhD, Lars H. Christensen, PhD, Kaare Lund, PhD
Experimental Immunology, ALK-Abelló, Hørsholm, Denmark 

Reprint requests: Jens Holm, PhD, Department of Experimental Immunology, ALK-Abelló, Bøge Allé 6-8 DK-2970 Hørsholm, Denmark.

Abstract

Background

The antibody repertoires of allergic subjects are characterized by the presence of allergen-specific IgE antibodies. We have previously shown that the composition of the IgE repertoire is critical for allergen-mediated activation of human effector cells. Activation of CD4+ T cells in allergic subjects is highly potentiated by the process of facilitated antigen presentation (FAP), in which allergen in complex with IgE is taken up by B cells through the low-affinity IgE receptor CD23 and presented to T cells.

Objective

We sought to investigate the influence of IgE repertoire complexity on the formation of IgE/allergen/CD23 complexes on B cells and subsequent T-cell activation.

Methods

Using defined allergen-specific recombinant IgE and IgG antibodies, we investigated the influence of individual IgE affinity, IgE clonality, specific IgE concentration, and the ratio between IgE specificities on IgE/allergen/CD23 complex formation in vitro.

Results

Although IgE affinity is an important factor, IgE clonality seems to be governing complex formation, especially with medium- and low-affinity IgE antibodies. We demonstrate that differences in allergen-specific IgE affinity correlate with the efficiency of subsequent T-cell activation. In addition, we show that the complexity of an IgE repertoire also affects the ability of allergen-specific IgG antibodies to block FAP.

Conclusion

The composition of allergen-specific IgE repertoires in individual patients, especially with respect to IgE clonality, might play an important role in the manifestation of allergic disease not only for the immediate allergic reaction through activation of basophils and mast cells but also for the exacerbation of allergic inflammation through recurring activation of allergen-specific T cells by FAP.

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Key words : Allergy, allergen, rIgE, rIgG, antibody repertoire, antibody-binding affinity, antibody clonality, blocking IgG, facilitated antigen presentation, T-cell activation

Abbreviations used : FAP, h, l, m, SIT


Esquema


 Disclosure of potential conflict of interest: J. Holm is employed by and owns shares in ALK-Abelló. P. A. Würtzen is employed by, owns shares in, and is an employee-elected board member for ALK-Abelló. L. H. Christensen is employed by, owns shares in, and receives research support from ALK-Abelló. K. Lund is employed by and owns shares in ALK-Abelló. N. Willumsen has declared that he has no conflict of interest.


© 2011  American Academy of Allergy, Asthma & Immunology. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 127 - N° 4

P. 1029-1037 - avril 2011 Regresar al número
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