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T Cell Epitope-Containing Domains of Ragweed Amb a 1 and Mugwort Art v 6 Modulate Immunologic Responses in Humans and Mice.
PLoS One. 2017; 12(1):e0169784.Plos

Abstract

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.

Authors+Show Affiliations

Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.Allergieambulatorium, Reumannplatz, Vienna, Austria.Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria. Christian Doppler Laboratory for Immunomodulation, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28081194

Citation

Sancho, Ana I., et al. "T Cell Epitope-Containing Domains of Ragweed Amb a 1 and Mugwort Art V 6 Modulate Immunologic Responses in Humans and Mice." PloS One, vol. 12, no. 1, 2017, pp. e0169784.
Sancho AI, Wallner M, Hauser M, et al. T Cell Epitope-Containing Domains of Ragweed Amb a 1 and Mugwort Art v 6 Modulate Immunologic Responses in Humans and Mice. PLoS ONE. 2017;12(1):e0169784.
Sancho, A. I., Wallner, M., Hauser, M., Nagl, B., Himly, M., Asam, C., Ebner, C., Jahn-Schmid, B., Bohle, B., & Ferreira, F. (2017). T Cell Epitope-Containing Domains of Ragweed Amb a 1 and Mugwort Art v 6 Modulate Immunologic Responses in Humans and Mice. PloS One, 12(1), e0169784. https://doi.org/10.1371/journal.pone.0169784
Sancho AI, et al. T Cell Epitope-Containing Domains of Ragweed Amb a 1 and Mugwort Art V 6 Modulate Immunologic Responses in Humans and Mice. PLoS ONE. 2017;12(1):e0169784. PubMed PMID: 28081194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - T Cell Epitope-Containing Domains of Ragweed Amb a 1 and Mugwort Art v 6 Modulate Immunologic Responses in Humans and Mice. AU - Sancho,Ana I, AU - Wallner,Michael, AU - Hauser,Michael, AU - Nagl,Birgit, AU - Himly,Martin, AU - Asam,Claudia, AU - Ebner,Christof, AU - Jahn-Schmid,Beatrice, AU - Bohle,Barbara, AU - Ferreira,Fatima, Y1 - 2017/01/12/ PY - 2016/07/13/received PY - 2016/12/21/accepted PY - 2017/1/13/entrez PY - 2017/1/13/pubmed PY - 2017/8/25/medline SP - e0169784 EP - e0169784 JF - PloS one JO - PLoS ONE VL - 12 IS - 1 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/28081194/T_Cell_Epitope_Containing_Domains_of_Ragweed_Amb_a_1_and_Mugwort_Art_v_6_Modulate_Immunologic_Responses_in_Humans_and_Mice_ L2 - http://dx.plos.org/10.1371/journal.pone.0169784 DB - PRIME DP - Unbound Medicine ER -