biostudies-literatureRoth-Walter FAustrian Science Fund FWF17416-21https://www.ebi.ac.uk/biostudies/studies/S-EPMC4067174biostudies-literatureUnknown289(25)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 bThe Journal of biological chemistryBet v 1 from birch pollen is a lipocalin-like protein acting as allergen only when devoid of iron by promoting Th2 lymphocytes.PMC4067174F 4606Mothes-Luksch NRoth GAPacios LFJensen-Jarolim ESinger JGomez-Casado CRoth-Walter FDiaz-Perales AfalseBet v 1 from birch pollen is a lipocalin-like protein acting as allergen only when devoid of iron by promoting Th2 lymphocytes.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 b2014-01-01T00:00:00Z2014 Jun2025-04-18T12:39:11.595Z2019-03-27T01:30:41ZS-EPMC40671742479832510.1074/jbc.M114.567875