Department of Chemistry, University of Eastern Finland, Joensuu, Finland.
PLoS One. 2010 Feb 5;5(2):e9037. doi: 10.1371/journal.pone.0009037.
Allergen-mediated cross-linking of IgE antibodies bound to the FcepsilonRI receptors on the mast cell surface is the key feature of the type I allergy. If an allergen is a homodimer, its allergenicity is enhanced because it would only need one type of antibody, instead of two, for cross-linking.
METHODOLOGY/PRINCIPAL FINDINGS: An analysis of 55 crystal structures of allergens showed that 80% of them exist in symmetric dimers or oligomers in crystals. The majority are transient dimers that are formed at high protein concentrations that are reached in cells by colocalization. Native mass spectrometric analysis showed that native allergens do indeed form transient dimers in solution, while hypoallergenic variants of them exist almost solely in the monomeric form. We created a monomeric Bos d 5 allergen and show that it has a reduced capability to induce histamine release.
CONCLUSIONS/SIGNIFICANCE: The results suggest that dimerization would be a very common and essential feature for allergens. Thus, the preparation of purely monomeric variants of allergens could open up novel possibilities for specific immunotherapy.
过敏原介导的 IgE 抗体与肥大细胞表面的 FcepsilonRI 受体结合的交联是 I 型过敏的关键特征。如果过敏原是同源二聚体,其变应原性会增强,因为它只需要一种类型的抗体而不是两种来交联。
方法/主要发现:对 55 个过敏原晶体结构的分析表明,它们中有 80%以对称二聚体或多聚体的形式存在于晶体中。大多数是瞬态二聚体,在细胞中通过共定位形成高蛋白质浓度时形成。天然质谱分析表明,天然过敏原确实在溶液中形成瞬态二聚体,而它们的低变应原性变体几乎仅以单体形式存在。我们创建了一个单体 Bos d 5 过敏原,并表明它诱导组胺释放的能力降低。
结论/意义:结果表明二聚化将是过敏原非常常见和必要的特征。因此,过敏原的纯单体变体的制备可能为特异性免疫治疗开辟新的可能性。