Dissection of immunoglobulin E and T lymphocyte reactivity of isoforms of the major birch pollen allergen Bet v 1: potential use of hypoallergenic isoforms for immunotherapy.
Dissection of immunoglobulin E and T lymphocyte reactivity of isoforms of the major birch pollen allergen Bet v 1: potential use of hypoallergenic isoforms for immunotherapy.
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DOI：
10.1084/jem.183.2.599
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发表时间：
1996-02-01
期刊：
影响因子：
--
通讯作者：
Ebner C
中科院分区：
文献类型：
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作者：
Ferreira F;Hirtenlehner K;Jilek A;Godnik-Cvar J;Breiteneder H;Grimm R;Hoffmann-Sommergruber K;Scheiner O;Kraft D;Breitenbach M;Rheinberger HJ;Ebner C
我们解剖了T细胞活化能力和免疫球蛋白（IG）E-结合特性（变应原性）的9种亚型的Bet v 1（Bet v 1a-Bet v 1 l），主要的桦树花粉过敏原。免疫印迹实验表明，Bet V 1亚型不同的能力，结合IgE从桦树花粉过敏患者。所有受试患者对每种特定亚型均显示出相似的IgE结合模式。基于这些实验，我们将Betv 1亚型分为三类：具有高IgE结合活性的分子（亚型a、e和j）、中等IgE结合活性的分子（亚型B、c和f）和低/无IgE结合活性的分子（亚型d、g和1）。Bet v 1a是一种从cDNA表达文库中筛选出的重组同种型，具有最高的IgE结合活性。从三个类别中选择亚型a、B、d、e和1作为实验的代表。使用外周血单核细胞、变应原特异性T细胞系和肽图谱变应原特异性T细胞克隆，测定了每种同种变应原激活桦树花粉过敏患者T淋巴细胞的效力。在这些患者中，一些人显示出对Bet v 1同种型的广泛的T细胞识别模式，而另一些人似乎仅限于特定的同种型。尽管存在这种变异性，但在同种型d（低IgE结合物）中观察到T细胞增殖应答的最高评分，其次是B、1、e和a。体内（皮肤点刺）试验表明，亚型d和1在Bet v 1过敏个体中诱导典型1型荨麻疹反应的效力显著低于亚型a、B和e。两者合计，我们的研究结果表明，低变应原性的Bet v 1亚型是变应原特异性T淋巴细胞的有效激活剂，并且具有高体外IgE结合活性和体内变应原性的Bet v 1亚型可以显示低的T细胞抗原性。基于这些发现，我们提出了一种新的方法免疫治疗I型过敏：治疗高剂量的低过敏性亚型或特应性过敏原的重组变体。我们进行的假设，这一措施将调制的质量的T辅助细胞在体内过敏原的反应。该治疗形式还将降低过敏性副作用的风险。
We dissected the T cell activation potency and the immunoglobulin (Ig) E-binding properties (allergenicity) of nine isoforms of Bet v 1 (Bet v 1a-Bet v 1l), the major birch pollen allergen. Immunoblot experiments showed that Bet v 1 isoforms differ in their ability to bind IgE from birch pollen-allergic patients. All patients tested displayed similar IgE-binding patterns toward each particular isoform. Based on these experiments, we grouped Bet v 1 isoforms in three classes: molecules with high IgE-binding activity (isoforms a, e, and j), intermediate IgE- binding (isoforms b, c, and f), and low/no IgE-binding activity (isoforms d, g, and 1). Bet v 1a, a recombinant isoform selected from a cDNA expression library using IgE immunoscreening exhibited the highest IgE-binding activity. Isoforms a, b, d, e, and 1 were chosen as representatives from the three classes for experimentation. The potency of each isoallergen to activate T lymphocytes from birch pollen- allergic patients was assayed using peripheral blood mononuclear cells, allergen-specific T cell lines, and peptide-mapped allergen-specific T cell clones. Among the patients, some displayed a broad range of T cell- recognition patterns for Bet v 1 isoforms whereas others seemed to be restricted to particular isoforms. In spite of this variability, the highest scores for T cell proliferative responses were observed with isoform d (low IgE binder), followed by b, 1, e, and a. In vivo (skin prick) tests showed that the potency of isoforms d and 1 to induce typical urticarial type 1 reactions in Bet v 1-allergic individuals was significantly lower than for isoforms a, b, and e. Taken together, our results indicate that hypoallergenic Bet v 1 isoforms are potent activators of allergen-specific T lymphocytes, and Bet v 1 isoforms with high in vitro IgE-binding activity and in vivo allergenicity can display low T cell antigenicity. Based on these findings, we propose a novel approach for immunotherapy of type I allergies: a treatment with high doses of hypoallergenic isoforms or recombinant variants of atopic allergens. We proceed on the assumption that this measure would modulate the quality of the T helper cell response to allergens in vivo. The therapy form would additionally implicate a reduced risk of anaphylactic side effects.