Bet v 1 from Birch Pollen is a Lipocalin-like Protein acting as Allergen only when devoid of Iron by promoting Th2 lymphocytes. [Protein Structure and Folding]

May 7th, 2014 by Roth-Walter, F., Gomez-Casado, C., Pacios, L. F., Mothes-Luksch, N., Roth, G. A., Singer, J., Diaz-Perales, A., Jensen-Jarolim, E.

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 immune-regulatory 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 66nM outpassed affinities to known ligands nearly by a power of ten. Moreover, we give functional evidence of the immune-modulatory 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.
  • Posted in Journal of Biological Chemistry, Publications
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