Abstract
Cyclophilin (Cyp) allergens are considered pan-allergens due to frequently reported cross-reactivity. In addition to well studied fungal Cyps, a number of plant Cyps were identified as allergens (e.g. Bet v 7 from birch pollen, Cat r 1 from periwinkle pollen). However, there are conflicting data regarding their antigenic/allergenic cross-reactivity, with no plant Cyp allergen structures available for comparison. Because amino acid residues are fairly conserved between plant and fungal Cyps, it is particularly interesting to check whether they can cross-react. Cat r 1 was identified by immunoblotting using allergic patients' sera followed by N-terminal sequencing. Cat r 1 (∼ 91% sequence identity to Bet v 7) was cloned from a cDNA library and expressed in Escherichia coli. Recombinant Cat r 1 was utilized to confirm peptidyl-prolyl cis-trans-isomerase (PPIase) activity by a PPIase assay and the allergenic property by an IgE-specific immunoblotting and rat basophil leukemia cell (RBL-SX38) mediator release assay. Inhibition-ELISA showed cross-reactive binding of serum IgE from Cat r 1-allergic individuals to fungal allergenic Cyps Asp f 11 and Mala s 6. The molecular structure of Cat r 1 was determined by NMR spectroscopy. The antigenic surface was examined in relation to its plant, animal, and fungal homologues. The structure revealed a typical cyclophilin fold consisting of a compact β-barrel made up of seven anti-parallel β-strands along with two surrounding α-helices. This is the first structure of an allergenic plant Cyp revealing high conservation of the antigenic surface particularly near the PPIase active site, which supports the pronounced cross-reactivity among Cyps from various sources.
Highlights
Plant cyclophilin allergens are not well characterized
21374 JOURNAL OF BIOLOGICAL CHEMISTRY. This is the first structure of an allergenic plant Cyp revealing high conservation of the antigenic surface near the peptidyl-prolyl cis-trans-isomerase (PPIase) active site, which supports the pronounced cross-reactivity among Cyps from various sources
Crystal structures of fungal Cyps Mala s 6 and Asp f 11 have been solved, but there is no structural information on plant Cyp allergens, which is necessary for analyzing cross-reactive antigenic surface and structure-based epitope prediction
Summary
Plant cyclophilin allergens are not well characterized. Results: Cat r 1, an allergenic pollen cyclophilin cross-reactive to fungal cyclophilins, was immunologically and biochemically characterized. An NMR structure identified a protein surface conserved between Cat r 1, fungal, and animal cyclophilins. In addition to well studied fungal Cyps, a number of plant Cyps were identified as allergens (e.g. Bet v 7 from birch pollen, Cat r 1 from periwinkle pollen). NMR data have been deposited in the BioMagResBank database This is the first structure of an allergenic plant Cyp revealing high conservation of the antigenic surface near the PPIase active site, which supports the pronounced cross-reactivity among Cyps from various sources. A Cyp allergen was first identified nearly 20 years ago from birch pollen extract prepared in neutral to alkaline extraction conditions (pH 7.5– 8.5) [10] This pollen allergen was later purified, characterized, cloned, and named as Bet v 7 [11, 12]. The total number of currently identified Cyp allergens is limited, a large population of allergic subjects is potentially sensitized to Cyps from fungi and plants
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