{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:36:33Z","timestamp":1790328993100,"version":"4.1.0"},"reference-count":102,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Danube Allergy Research Cluster-DARC","award":["8"],"award-info":[{"award-number":["8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alternaria alternata is a common fungus strongly related with severe allergic asthma, with 80% of affected individuals being sensitized solely to its major allergen Alt a 1. Here, we assessed the function of Alt a 1 as an innate defense protein binding to micronutrients, such as iron\u2013quercetin complexes (FeQ2), and its impact on antigen presentation in vitro. Binding of Alt a 1 to FeQ2 was determined in docking calculations. Recombinant Alt a 1 was generated, and binding ability, as well as secondary and quaternary structure, assessed by UV-VIS, CD, and DLS spectroscopy. Proteolytic functions were determined by casein and gelatine zymography. Uptake of empty apo\u2013 or ligand-filled holoAlt a 1 were assessed in human monocytic THP1 cells under the presence of dynamin and clathrin-inhibitors, activation of the Arylhydrocarbon receptor (AhR) using the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for phenotypic changes in monocytes by flow cytometry. Alt a 1 bound strongly to FeQ2 as a tetramer with calculated Kd values reaching pico-molar levels and surpassing affinities to quercetin alone by a factor of 5000 for the tetramer. apoAlt a 1 but not holoAlta 1 showed low enzymatic activity against casein as a hexamer and gelatin as a trimer. Uptake of apo\u2013 and holo\u2013Alt a 1 occurred partly clathrin-dependent, with apoAlt a 1 decreasing labile iron in THP1 cells and holoAlt a 1 facilitating quercetin-dependent AhR activation. In human PBMCs uptake of holoAlt a 1 but not apoAlt a 1 significantly decreased the surface expression of the costimulatory CD86, but also of HLADR, thereby reducing effective antigen presentation. We show here for the first time that the presence of nutritional iron complexes, such as FeQ2, significantly alters the function of Alt a 1 and dampens the human immune response, thereby supporting the notion that Alt a 1 only becomes immunogenic under nutritional deprivation.<\/jats:p>","DOI":"10.3390\/ijms241511934","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:45:02Z","timestamp":1690332302000},"page":"11934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Nutritional Provision of Iron Complexes by the Major Allergen Alt a 1 to Human Immune Cells Decreases Its Presentation"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6804-6238","authenticated-orcid":false,"given":"Aila","family":"Fakhimahmadi","sequence":"first","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute, 1210 Vienna, Austria"},{"name":"Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3039-4855","authenticated-orcid":false,"given":"Ilir","family":"Hasanaj","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2077-4479","authenticated-orcid":false,"given":"Gerlinde","family":"Hofstetter","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute, 1210 Vienna, Austria"},{"name":"Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Pogner","sequence":"additional","affiliation":[{"name":"Bioresources Unit, Center for Health & Bioresources, AIT Austrian Institute of Technology GmbH, 3430 Tulln, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-6044","authenticated-orcid":false,"given":"Markus","family":"Gorfer","sequence":"additional","affiliation":[{"name":"Bioresources Unit, Center for Health & Bioresources, AIT Austrian Institute of Technology GmbH, 3430 Tulln, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4750-4746","authenticated-orcid":false,"given":"Markus","family":"Wiederstein","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Szepannek","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0351-6937","authenticated-orcid":false,"given":"Rodolfo","family":"Bianchini","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3938-3585","authenticated-orcid":false,"given":"Zdenek","family":"Dvorak","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, Faculty of Science, Palacky University, 779 00 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian A.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Berger","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4019-5765","authenticated-orcid":false,"given":"Erika","family":"Jensen-Jarolim","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute, 1210 Vienna, Austria"},{"name":"Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Hufnagl","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute, 1210 Vienna, Austria"},{"name":"Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5005-9228","authenticated-orcid":false,"given":"Franziska","family":"Roth-Walter","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Interuniversity Messerli Research Institute, 1210 Vienna, Austria"},{"name":"Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.3389\/fpls.2018.01213","article-title":"Fungal Endophyte Alternaria tenuissima Can Affect Growth and Selenium Accumulation in Its Hyperaccumulator Host Astragalus bisulcatus","volume":"9","author":"Lindblom","year":"2018","journal-title":"Front. 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