T Cell Epitope-Containing Domains of Ragweed Amb a 1 and Mugwort Art v 6 Modulate Immunologic Responses in Humans and MiceReportar como inadecuado




T Cell Epitope-Containing Domains of Ragweed Amb a 1 and Mugwort Art v 6 Modulate Immunologic Responses in Humans and Mice - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Background

Ragweed Ambrosia artemisiifolia and mugwort Artemisia vulgaris are the major cause of pollen allergy in late summer. Allergen-specific lymphocytes are crucial for immune modulation during immunotherapy. We sought to generate and pre-clinically characterise highly immunogenic domains of the homologous pectate lyases in ragweed Amb a 1 and mugwort pollen Art v 6 for immunotherapy.

Methods

Domains of Amb a 1 Amb a 1α and Art v 6 Art v 6α and a hybrid molecule, consisting of both domains, were designed, expressed in E. coli and purified. Human IgE reactivity and allergenicity were assessed by ELISA and mediator release experiments using ragweed and mugwort allergic patients. Moreover, T cell proliferation was determined. Blocking IgG antibodies and cytokine production in BALB-c mice were studied by ELISA and ELISPOT.

Results

The IgE binding capacity and in vitro allergenic activity of the Amb a 1 and Art v 6 domains and the hybrid were either greatly reduced or abolished. The recombinant proteins induced T cell proliferative responses comparable to those of the natural allergens, indicative of retained allergen-specific T cell response. Mice immunisation with the hypoallergens induced IL-4, IL-5, IL-13 and IFN-γ production after antigen-specific in vitro re-stimulation of splenocytes. Moreover, murine IgG antibodies that inhibited specific IgE binding of ragweed and mugwort pollen allergic patients were detected.

Conclusion

Accumulation of T cell epitopes and deletion of IgE reactive areas of Amb a 1 and Art v 6, modulated the immunologic properties of the allergen immuno-domains, leading to promising novel candidates for therapeutic approach.



Autor: Ana I. Sancho , Michael Wallner, Michael Hauser, Birgit Nagl, Martin Himly, Claudia Asam, Christof Ebner, Beatrice Jahn-Schmid, B

Fuente: http://plos.srce.hr/



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