Takai T, Mori A, Yuuki T, Okudaira H, Okumura Y
Bioscience Research and Development Laboratory, Asahi Breweries Ltd., Ibaraki, Japan.
Mol Immunol. 1999 Oct-Nov;36(15-16):1055-65. doi: 10.1016/s0161-5890(99)00098-x.
Allergen-specific immunotherapy, in which repeated injections of allergens over prolonged periods are used to induce tolerance, has proven an effective treatment of allergy. A major side effect of allergen-specific immunotherapy is anaphylactic reaction. House dust mite allergens are major causative factors associated with various allergic diseases. Der f 2 is the major house dust mite allergen composed of 129 amino acid residues. Analysis using deletion mutants of Der f 2 suggested that T-cell epitopes of Der f 2 were multiple in mite-allergic patients. We found that some IgE epitopes were renatured by dialysis of a mixture of two denatured C- and N-terminal deletion mutants, 1-112 and 85-129 in 13 patients out of 14. On the other hand, IgE binding activity was negative in the separately dialyzed fragments and their mixture in each patient tested. Furthermore, we demonstrated that neither of the two separately prepared polypeptides induced in vivo skin prick test reactivity. These findings are important for improvement of T-cell targeting allergen-specific immunotherapy and development of monovalent IgE haptens. The use of combinations of overlapping non-anaphylactic fragments of allergen covering all of the T-cell epitopes achieves the removal of IgE reactivity, the cause of harmful anaphylactic reactions, without affecting the T-cell reactivity essential for immunotherapy, offering potentially safer and more effective treatment for allergic disease.
变应原特异性免疫疗法，即通过长时间重复注射变应原以诱导耐受，已被证明是一种有效的过敏治疗方法。变应原特异性免疫疗法的一个主要副作用是过敏反应。屋尘螨变应原是与各种过敏性疾病相关的主要致病因素。Der f 2是由129个氨基酸残基组成的主要屋尘螨变应原。对Der f 2缺失突变体的分析表明，在螨过敏患者中Der f 2的T细胞表位是多样的。我们发现，在14名患者中的13名患者中，通过对两种变性的C端和N端缺失突变体（1-112和85-129）的混合物进行透析，一些IgE表位得以复性。另一方面，在每个测试患者中，单独透析的片段及其混合物的IgE结合活性均为阴性。此外，我们证明，两种单独制备的多肽均未诱导体内皮肤点刺试验反应性。这些发现对于改进靶向T细胞的变应原特异性免疫疗法和开发单价IgE半抗原有重要意义。使用覆盖所有T细胞表位的变应原重叠非过敏片段组合，可消除有害过敏反应的起因IgE反应性，而不影响免疫疗法所必需的T细胞反应性，为过敏性疾病提供了潜在更安全、更有效的治疗方法。
