Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Institute for Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Allergy. 2023 Dec;78(12):3136-3153. doi: 10.1111/all.15865. Epub 2023 Sep 13.
The nature of epitopes on Bet v 1 recognized by natural IgG antibodies of birch pollen allergic patients and birch pollen-exposed but non-sensitized subjects has not been studied in detail.
To investigate IgE and IgG recognition of Bet v 1 and to study the effects of natural Bet v 1-specific IgG antibodies on IgE recognition of Bet v 1 and Bet v 1-induced basophil activation.
Sera from birch pollen allergic patients (BPA, n = 76), allergic patients without birch pollen allergy (NBPA, n = 40) and non-allergic individuals (NA, n = 48) were tested for IgE, IgG as well as IgG and IgG reactivity to folded recombinant Bet v 1, two unfolded recombinant Bet v 1 fragments comprising the N-terminal (F1) and C-terminal half of Bet v 1 (F2) and unfolded peptides spanning the corresponding sequences of Bet v 1 and the apple allergen Mal d 1 by ELISA or micro-array analysis. The ability of Bet v 1-specific serum antibodies from non-allergic subjects to inhibit allergic patients IgE or IgG binding to rBet v 1 or to unfolded Bet v 1-derivatives was assessed by competition ELISAs. Furthermore, the ability of serum antibodies from allergic and non-allergic subjects to modulate Bet v 1-induced basophil activation was investigated using rat basophilic leukaemia cells expressing the human FcεRI which had been loaded with IgE from BPA patients.
IgE antibodies from BPA patients react almost exclusively with conformational epitopes whereas IgG, IgG and IgG antibodies from BPA, NBPA and NA subjects recognize mainly unfolded and sequential epitopes. IgG competition studies show that IgG specific for unfolded/sequential Bet v 1 epitopes is not inhibited by folded Bet v 1 and hence the latter seem to represent cryptic epitopes. IgG reactivity to Bet v 1 peptides did not correlate with IgG reactivity to the corresponding Mal d 1 peptides and therefore does not seem to be a result of primary sensitization to PR10 allergen-containing food. Natural Bet v 1-specific IgG antibodies inhibited IgE binding to Bet v 1 only poorly and could even enhance Bet v 1-specific basophil activation.
IgE and IgG antibodies from BPA patients and birch pollen-exposed non-sensitized subjects recognize different epitopes. These findings explain why natural allergen-specific IgG do not protect against allergic symptoms and suggest that allergen-specific IgE and IgG have different clonal origin.
尚未详细研究桦树花粉过敏患者和桦树花粉暴露但未致敏的个体天然 IgG 抗体识别的 Bet v 1 表位的性质。
研究 Bet v 1 的 IgE 和 IgG 识别，并研究天然 Bet v 1 特异性 IgG 抗体对 Bet v 1 和 Bet v 1 诱导的嗜碱性粒细胞活化的 IgE 识别的影响。
用 ELISA 或微阵列分析检测桦树花粉过敏患者（BPA，n=76）、无桦树花粉过敏的过敏患者（NBPA，n=40）和非过敏个体（NA，n=48）的血清 IgE、IgG 以及 IgG 和 IgG 对折叠重组 Bet v 1、包含 Bet v 1 N 端（F1）和 C 端一半的两个未折叠重组 Bet v 1 片段（F2）以及跨越 Bet v 1 和苹果过敏原 Mal d 1 对应序列的未折叠肽的反应性。通过竞争 ELISA 评估非过敏个体的 Bet v 1 特异性血清抗体抑制过敏患者 IgE 或 IgG 与 rBet v 1 或未折叠 Bet v 1 衍生物结合的能力。此外，使用表达 BPA 患者 IgE 的大鼠嗜碱性白血病细胞研究过敏和非过敏个体的血清抗体调节 Bet v 1 诱导的嗜碱性粒细胞活化的能力。
BPA 患者的 IgE 抗体几乎仅与构象表位反应，而 BPA、NBPA 和 NA 患者的 IgG、IgG 和 IgG 抗体主要识别未折叠和顺序表位。IgG 竞争研究表明，针对未折叠/顺序 Bet v 1 表位的 IgG 特异性不受折叠 Bet v 1 的抑制，因此后者似乎代表隐匿表位。Bet v 1 肽的 IgG 反应性与相应的 Mal d 1 肽的 IgG 反应性无关，因此似乎不是对包含 PR10 过敏原的食物的初次致敏的结果。天然 Bet v 1 特异性 IgG 抗体对 IgE 与 Bet v 1 的结合抑制作用较差，甚至可以增强 Bet v 1 特异性嗜碱性粒细胞活化。
BPA 患者和桦树花粉暴露未致敏的个体的 IgE 和 IgG 抗体识别不同的表位。这些发现解释了为什么天然过敏原特异性 IgG 不能预防过敏症状，并表明过敏原特异性 IgE 和 IgG 具有不同的克隆起源。
