Detailed understanding of how Abs of the IgE isotype interact with allergen at the onset of an allergic reaction is of great importance for deciphering mechanisms involved in the development of disease and may aid in the design of hypoallergenic variants. In this study, we have used a set of human monoclonal IgE Abs derived from the repertoires of allergic individuals, specific for the major timothy grass pollen allergen Phl p 1, to gain detailed information on the interaction between Abs and allergen. These allergen-specific IgE are to varying degrees cross-reactive toward both different allergen isoforms and various group 1 allergens originating from other grass species. The usage of human monoclonal IgE, as an alternative to polyclonal preparations or mouse Abs, allowed us to locate several important IgE-binding epitopes on the C-terminal domain of Phl p 1, all clustered to an IgE-binding “hot spot.” By introducing three mutations in the IgE-binding area of the C-terminal domain we were able to significantly reduce its reactivity with serum IgE. In conclusion, our study shows the great potential of using human monoclonal IgE as a tool for studies of the molecular interactions taking place during allergic responses. Furthermore, we present a novel IgE-hyporeactive fragment with the potential to be used as a safer hypoallergenic alternative in specific immunotherapy than the pollen extracts used today.
Decreased frequency of intracellular IFN-gamma producing T cells in whole blood preparations from patients with atopic dermatitis.Källström, Eva; Roscher, Ingrid; Andreasson, Annica; Bäck, Ove; Van Hage-Hamsten, MariannePublished in: Experimental Dermatology DOI: 10.1034/j. 1600-0625.2002.110608.x 2002 Link to publication Citation for published version (APA): Källström, E., Roscher, I., Andreasson, A., Bäck, O., & Van Hage-Hamsten, M. (2002). Decreased frequency of intracellular IFN-gamma producing T cells in whole blood preparations from patients with atopic dermatitis. Experimental Dermatology, 11(6), 556-563. https://doi.org/10.1034/j. 1600-0625.2002.110608.x General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. severity and the level of total IgE (r Ω 0.67, P Ͻ 0.05). In conclusion, our e-mail: marianne.van.hage.hamsten/ks.se results support the evidence for a decreased ability of peripheral CD4 π T cells to produce IFN-g among AD patients.
In this study we have for the first time shown that the predatory mites P. persimilis and H. miles can cause IgE-mediated sensitization among greenhouse workers. The clinical relevance of sensitization to predatory mites needs to be investigated in further studies.
BackgroundGroup 5 allergens are small proteins that consist of two domains. They belong to the most potent respiratory allergens.ObjectiveTo determine the binding sites and to study allergic patients' IgE recognition of the group 5 allergen (Phl p 5) from timothy grass pollen using human monoclonal IgE antibodies that have been isolated from grass pollen allergic patients.MethodsUsing recombinant isoallergens, fragments, mutants and synthetic peptides of Phl p 5, as well as peptide-specific antibodies, the interaction of recombinant human monoclonal IgE and Phl p 5 was studied using direct binding and blocking assays. Cross-reactivity of monoclonal IgE with group 5 allergens in several grasses was studied and inhibition experiments with patients' polyclonal IgE were performed.ResultsMonoclonal human IgE showed extensive cross-reactivity with group 5 allergens in several grasses. Despite its small size of 29 kDa, four independent epitope clusters on isoallergen Phl p 5.0101, two in each domain, were recognized by human IgE. Isoallergen Phl p 5.0201 carried two of these epitopes. Inhibition studies with allergic patients' polyclonal IgE suggest the presence of additional IgE epitopes on Phl p 5.Conclusions & Clinical RelevanceOur results reveal the presence of a large number of independent IgE epitopes on the Phl p 5 allergen explaining the high allergenic activity of this protein and its ability to induce severe allergic symptoms. High-density IgE recognition may be a general feature of many potent allergens and form a basis for the development of improved diagnostic and therapeutic procedures in allergic disease.
The pathophysiology of asthma is complex and engages cascades of events in the cytokine network. We, therefore, investigated the impact of bronchial allergen challenge in humans on the cytokine profile of circulating lymphocytes. Peripheral blood samples from 10 patients with allergic asthma were collected before and 24 h after allergen provocation. Patients who mounted a late-phase reaction were designated dual responders opposite to single responders. Whole blood cells were stimulated by mitogen and intracellular interleukin (IL)-4 and interferon (IFN)-g were detected by flow cytometry. The allergen challenge induced a decrease in IL-4 þ CD4 þ cells in the patients (P ¼ 0.05), and a significant decrease (P < 0.05) in IFN-g þ CD4 þ cells was noted in single, but not dual, responders. In addition, there was a significant difference (P < 0.01) with respect to the changes in the IFN-g þ CD4þ cells comparing dual and single responders. No corresponding changes were observed in CD8 þ cells. The data suggest a possible on-going traffic of IFN-g and IL-4 þ CD4 þ lymphocytes into the bronchial mucosa in relation to an allergen challenge and generate the hypothesis that a difference exists between single and dual responders in this respect. Because the CD4 þ IFN-g-producing cells have the capacity to downregulate the T-helper type 2 response, a reduced capacity in this aspect might contribute to the pathophysiology in dual responders.
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