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Organization of two invariant surface glycoproteins in the surface coat of Trypanosoma brucei.

机译:布氏锥虫的表皮中两个不变的表面糖蛋白的组织。

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The surface coat of Trypanosoma brucei, formed by about 10(7) molecules of the membrane-form variant surface glycoprotein (mfVSG) per cell, is generally considered to constitute a barrier against the access of antibodies directed to invariant surface proteins. The recent characterization of two invariant surface glycoproteins (ISGs) with apparent molecular masses of 65 and 75 kDa (ISG65 and ISG75; 70,000 and 50,000 molecules per cell, respectively), which are both predicted to be composed of large extracellular domains, single transmembrane alpha-helices, and small intracellular domains, enabled a critical test of this hypothesis. Although ISG65 is distributed over the entire surface of the parasites, it is not accessible to antibodies or to the proteinase trypsin in live cells provided the mfVSG is also proteinase resistant. ISG75 is similarly distributed; its accessibility to antibodies depends on the expressed mfVSG, and it is sensitive to trypsin in a variant clone in which the mfVSG is proteinase resistant. Vaccination experiments using recombinant proteins to a mixture of the native ISGs were unsuccessful. ISG65 but not ISG75 elicited an antibody response in chronically infected mice. The results strengthen the view of the protective properties of the variant surface glycoprotein coat by steric hindrance and suggest that additional factors such as low abundance or low immunogenicity of invariant surface proteins may prevent a control of the disease by the humoral immune response.
机译:通常认为布氏锥虫的表面涂层由每个细胞的约10(7)个分子的膜形式变体表面糖蛋白(mfVSG)分子形成,构成了针对针对不变表面蛋白的抗体访问的屏障。最近表征的两种不变表面糖蛋白(ISG)的表观分子量分别为65和75 kDa(ISG65和ISG75;每个细胞分别为70,000和50,000分子),它们均由大的细胞外结构域,单个跨膜α组成-螺旋和小的细胞内结构域使对该假设的关键检验成为可能。尽管ISG65分布在寄生虫的整个表面上,但如果mfVSG也具有蛋白酶抗性,则抗体或蛋白酶不能被活细胞中的胰蛋白酶消化。 ISG75的分发方式与此类似;它对抗体的可及性取决于表达的mfVSG,并且对mfVSG具有蛋白酶抗性的变体克隆中的胰蛋白酶敏感。使用重组蛋白对天然ISG混合物进行的疫苗接种实验未成功。在长期感染的小鼠中,ISG65而非ISG75引发抗体反应。结果加强了对通过空间位阻的变体表面糖蛋白被膜的保护特性的看法,并暗示了诸如不变表面蛋白的低丰度或低免疫原性等其他因素可能会阻止通过体液免疫反应控制疾病。

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