Department of Pediatrics, Philipps University, Marburg, Germany.
Int Arch Allergy Immunol. 2011;156(3):247-58. doi: 10.1159/000323527. Epub 2011 Jun 29.
We have previously shown that the allergic sensitization to ovalbumin does not represent a superantigen-like immune response. In gene-targeted mice (ΔD-iD) with a single modified Diversity gene segment (D(H)) of the immunoglobulin heavy chain, enriched for charged amino acids, the asthma phenotype in a murine model was markedly alleviated compared to wild-type animals.
We now sought to determine whether the confinement to a single D(H) gene segment alone leads to a reduced allergic phenotype.
We examined another gene-targeted mouse strain (ΔD-DFL) with a single D(H) gene segment which encodes for neutral amino acids, thus reflecting the preferential repertoire in wild-type mice. Mice were sensitized intraperitoneally to ovalbumin.
Despite the constraint to a single D(H) gene segment, ΔD-DFL mice mounted high total and allergen-specific IgG(1) and IgE serum levels after sensitization to ovalbumin. The affinity constants of allergen-specific IgG(1) antibodies did not differ between ΔD-DFL and wild type. Following challenge with aerosolized allergen, a marked local T(H)2 cytokine response and an eosinophilic airway inflammation developed. Quantitative histology revealed increased mucus production and intense goblet cell metaplasia which were identical to those in wild type. Moreover, ΔD-DFL mice developed an airway hyperreactivity to methacholine and to the specific allergen, which both did not differ from those in wild-type animals.
A single D(H) gene segment is sufficient for the establishment of the asthma phenotype in a murine model of allergic airway inflammation. Thus, the allergic phenotype depends on the amino acid composition and not on the diversity of the classical antigen-binding site.
我们之前已经表明，卵清蛋白的过敏致敏并不代表超抗原样免疫反应。在具有单一修饰的免疫球蛋白重链多样性基因片段（D（H））的基因靶向小鼠（ΔD-iD）中，富含带电荷的氨基酸，与野生型动物相比，哮喘表型在鼠模型中明显减轻。
我们现在试图确定仅局限于单个 D（H）基因片段是否会导致过敏表型降低。
我们研究了另一种基因靶向小鼠（ΔD-DFL），其具有编码中性氨基酸的单个 D（H）基因片段，因此反映了野生型小鼠中的优先库。将小鼠用卵清蛋白经腹腔致敏。
尽管局限于单个 D（H）基因片段，ΔD-DFL 小鼠在对卵清蛋白致敏后仍能产生高总和过敏原特异性 IgG（1）和 IgE 血清水平。过敏原特异性 IgG（1）抗体的亲和力常数在ΔD-DFL 和野生型之间没有差异。在用雾化过敏原进行攻击后，会出现明显的局部 T（H）2细胞因子反应和嗜酸性气道炎症。定量组织学显示粘液产生增加和强烈的杯状细胞化生，与野生型相同。此外，ΔD-DFL 小鼠对乙酰甲胆碱和特异性过敏原表现出气道高反应性，与野生型动物没有差异。
在过敏性气道炎症的鼠模型中，单个 D（H）基因片段足以建立哮喘表型。因此，过敏表型取决于氨基酸组成，而不是经典抗原结合位点的多样性。
