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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Recombinant Allergnes with Reduced Allergenicity but Retaining Immunogenicity of the Natural Allergens:Hybrids of Yellow Jacket and paper Wasp Venom Allergen Antigen 5s
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Recombinant Allergnes with Reduced Allergenicity but Retaining Immunogenicity of the Natural Allergens:Hybrids of Yellow Jacket and paper Wasp Venom Allergen Antigen 5s

机译:重组变应原,具有降低的变应原性但保留了天然变应原的免疫原性:黄夹克和纸黄蜂毒液变应原抗原5s的混合体

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摘要

Ihe homologous venom allergen Ag 5s from the yellow jacket (Vespula vulgaris) and paper wasp (Polistes annularis) have 59% ~uence identity of their respective 204 and 205 amino acid residues, and they have low degrees of antigenic cross-reactivity in meCt allergic patients and in animal models. Hybrids containing different segments of these two vespid Ag 5s were expressed in ~mst. Circular dichroism spectroscopy suggests the hybrids to have the secondary structure of natural Ag 5. Inhibition ELISA ~kh human and murine Abs suggests the hybrids to have the discontinuous B cell epitopes of the natural Ag 5 but with an altered ~itope density. The hybrids were immunogenic in mice for B and T cell responses to both Ag 5s. The N-terminal region of Ag was found to contain its dominant B cell epitope(s). Hybrids containing 10—49 residues of yellow jacket Ag 5 showed 100- to OO-fold reduction in allergenicity when tested by histamine release assay with basophils of yellow jacket-sensitive patients. Our ~Iings suggest that hybrids represent a useful approach to map the discontinuous B cell epitope-containing regions of proteins. rhey also suggest that Ag 5 hybrids may be useful immunotherapeutic reagents in man.
机译:黄夹克(Vespula vulgaris)和黄蜂(Polistes ringis)的同源毒变应原Ag 5s在各自的204和205个氨基酸残基上具有59%的同一性,并且在meCt变应原中的抗原交叉反应性较低患者和动物模型。包含这两个小孢子Ag 5s不同片段的杂种在mst中表达。圆二色光谱表明杂种具有天然Ag 5的二级结构。人和鼠Abs的抑制ELISA表明杂种具有天然Ag 5的不连续B细胞表位,但其表观密度改变。杂种在小鼠中对两种Ag 5s的B和T细胞应答均具有免疫原性。发现Ag的N-末端区域包含其主要的B细胞表位。当通过对黄色夹克敏感患者的嗜碱性粒细胞进行组胺释放测定进行测试时,含有黄色夹克Ag 5 10-49残基的杂种显示出100%至OO倍的变应原性降低。我们的结论表明,杂合体代表了一种有用的方法来定位蛋白质中不连续的B细胞表位区域。 Rhey还表明,Ag 5杂种可能是人类有用的免疫治疗剂。

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