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Gewählte Publikation:

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Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2014

AutorInnen: Roth-Walter, F; Gomez-Casado, C; Pacios, LF; Mothes-Luksch, N; Roth, GA; Singer, J; Diaz-Perales, A; Jensen-Jarolim, E

Titel: Bet v 1 from birch pollen is a lipocalin-like protein acting as allergen only when devoid of iron by promoting Th2 lymphocytes.

Quelle: J Biol Chem. 2014; 289(25):17416-17421



Autor/innen der Vetmeduni Vienna:

Jensen-Jarolim Erika
Roth-Walter Franziska

Beteiligte Vetmed-Organisationseinheiten
Messerli Forschungsinstitut, Abteilung für Komparative Medizin


Abstract:
It is hypothesized that allergens are at the borderline of self and non-self and, through as yet elusive circumstances, mount a Th2 response for allergic sensitization. The major birch pollen allergen Bet v 1 is considered the prototype for the PR-10 protein family causing respiratory allergy. Here, we give structural evidence that Bet v 1 is a lipocalin-like protein with a striking structural resemblance to human lipocalin 2. Lipocalin 2 is highly expressed in the lung where it exerts immunoregulatory functions dependent on being loaded with siderophore-bound iron (holo-form) or not (apo-form). We demonstrate that similar to lipocalin 2, Bet v 1 is capable of binding iron via catechol-based siderophores. Thereby, calculated Kd values of 66 nm surpassed affinities to known ligands nearly by a power of 10. Moreover, we give functional evidence of the immunomodulatory capacity of Bet v 1 being dependent on its iron-loaded state. When incubated to human immune cells, only the apo-form of Bet v 1, but not the holo-form, was able to promote Th2 cells secreting IL13. These results provide for the first time a functional understanding on the allergenicity of Bet v 1 and a basis for future allergen immunotherapies counteracting Th2 immune responses on a molecular basis.

Keywords Pubmed: Acute-Phase Proteins*
Antigens, Plant*/chemistry
Antigens, Plant*/genetics
Antigens, Plant*/immunology
Betula*/chemistry
Betula*/genetics
Betula*/immunology
Cells, Cultured
Female
Humans
Hypersensitivity/genetics
Hypersensitivity/immunology
Iron*/chemistry
Iron*/immunology
Lipocalins*
Male
Proto-Oncogene Proteins*
Structural Homology, Protein
Th2 Cells/immunology*
Th2 Cells/pathology


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