Friday, July 17, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Franziska Roth-Walter, PhD
,
Messerli Research Institute, Vienna, Austria
Cristina Gomez-Casado, PhD
,
Biotechnology Department, Center for Plant Biotechnology and Genomics, Technical University of Madrid, Madrid, Spain
Luis F Pacios, PhD
,
Department of Natural Resources and Systems, ETSI Montes, Technical University of Madrid, Madrid, Spain
Nadine Mothes-Luksch, MD
,
AllergyCare, Vienna, Austria
Georg A Roth, MD
,
Department of Anesthesiology, General Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria
Josef Singer, MD PhD
,
Comparative Immunology and Oncology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
Araceli Diaz-Perales, PhD
,
Biotechnology Department, Center for Plant Biotechnology and Genomics, Technical University of Madrid, Madrid, Spain
Erika Jensen-Jarolim, MD
,
Comparative Immunology and Oncology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
The major birch pollen allergen, Bet v 1, causes respiratory allergy through yet still elusive circumstances. On the other hand, in the lung the human lipocalin-2, LCN2 is highly expressed and has immune-regulatory properties depending whether it carries iron via siderophores (holo-) or not (apo-). In this respect, we investigated Bet v 1, for its structural and biological resemblance with LCN2.
FATCATflex, CE (Combinatorial Extention) algorithm and TM (Template Modeling) Align structural comparison methods indicate that Bet v 1 structure bears a significant resemblance to lipocalins. Prussian blue-staining as well as in silico docking analyses reveal that, similarly to lipocalins, the birch allergen is also capable of binding iron via catechol-based siderophores. Calculated Kd-values of 20nM outpassed affinities to known ligands more than twentyfold. When incubated with activated PBMCs (n=10), only the apo-form of Bet v 1, but not the holo-form, increased CD4+ expression in T cells and the secretion of IL13.
Our work supports the claim that Bet v 1 may be considered a lipocalin-like protein capable of binding iron via siderophores. We give for the first time evidence that the form of application (apo- or holo-) is decisive for the subsequent immune response. The apo-form promotes Th2 cells, whereas the holo-form appears immunosuppressive. These results provide for the first time a functional understanding on the allergenicity of Bet v 1.
