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Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2018

AutorInnen: Hufnagl, K; Ghosh, D; Wagner, S; Fiocchi, A; Dahdah, L; Bianchini, R; Braun, N; Steinborn, R; Hofer, M; Blaschitz, M; Roth, GA; Hofstetter, G; Roth-Walter, F; Pacios, LF; Jensen-Jarolim, E

Titel: Retinoic acid prevents immunogenicity of milk lipocalin Bos d 5 through binding to its immunodominant T-cell epitope.

Quelle: Sci Rep. 2018; 8(1):1598



Autor/innen der Vetmeduni Vienna:

Bianchini Rodolfo
Braun Nina
Hofer Martin
Hofstetter Gerlinde
Hufnagl Karin
Jensen-Jarolim Erika
Roth-Walter Franziska
Steinborn Ralf

Beteiligte Vetmed-Organisationseinheiten
Messerli Forschungsinstitut, Abteilung für Komparative Medizin
VetCore


Zugehörige(s) Projekt(e): Entwicklung von Mimotop-Vakzinen für präklinische und komparative Medizin Studien


Abstract:
The major cow's milk allergen Bos d 5 belongs to the lipocalin protein family, with an intramolecular pocket for hydrophobic ligands. We investigated whether Bos d 5 when loaded with the active vitamin A metabolite retinoic acid (RA), would elicit differential immune responses compared to the unloaded state. By in silico docking an affinity energy of -7.8 kcal/mol was calculated for RA into Bos d 5. Loading of RA to Bos d 5 could be achieved in vitro, as demonstrated by ANS displacement assay, but had no effect on serum IgE binding in tolerant or challenge-positive milk allergic children. Bioinformatic analysis revealed that RA binds to the immunodominant T-cell epitope region of Bos d 5. In accordance, Bos d 5 significantly suppressed the CD3+ CD4+ cell numbers, proliferative response and IL-10, IL-13 and IFN-γ secretion from stimulated human PBMCs only when complexed with RA. This phenomenon was neither associated with apoptosis of T-cells nor with the activation of Foxp3+ T-cells, but correlated likely with enhanced stability to lysosomal digestion due to a predicted overlap of Cathepsin S cleavage sites with the RA binding site. Taken together, proper loading of Bos d 5 with RA may suppress its immunogenicity and prevent its allergenicity.

Keywords Pubmed: Allergensimmunologymetabolism
Animals
Cattle
Cell Proliferationdrug effects
Epitopes, T-Lymphocytemetabolism
Humans
Immunoglobulin Emetabolism
Immunologic Factorsmetabolism
Interferon-gammametabolism
Interleukin-10metabolism
Interleukin-13metabolism
Leukocytes, Mononuclearimmunology
Lipocalinsimmunologymetabolism
Lysosomesmetabolism
Molecular Docking Simulation
Protein Binding
Proteolysis
Tretinoinmetabolism

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