Reinitz D M, Aizenstein B D, Mansfield J M
Department of Veterinary Science, University of Wisconsin, Madison 53706.
Mol Biochem Parasitol. 1992 Mar;51(1):119-32. doi: 10.1016/0166-6851(92)90207-z.
The characterization of B cell epitopes on the trypanosome variant surface glycoprotein (VSG) rests on elucidation of variant specific amino acid sequences that may be exposed or buried as a result of the natural conformation of these molecules in the surface coat. Despite the fact that different VSGs have heterogeneous primary sequences and unique antigenic characteristics, recent high resolution X-ray crystallographic analyses of VSGs have revealed a conserved 3-dimensional structure common to these surface proteins [19]. We took advantage of this conserved structural conformation to help predict which variant subregions of VSG molecules may contain exposed or buried variant specific B cell epitopes. Using Staden data tables, we aligned the deduced amino acid sequence of Trypanosoma brucei rhodesiense LouTat 1 VSG, a molecule that has been characterized immunologically in this laboratory, with 12 other complete VSG sequences including the T. b. brucei MiTat 1.2 VSG that has been characterized in crystallographic studies. Results of this analysis predict that there are eight defined clusters of variant amino acids which may contribute to exposed B cell epitopes, and ten defined clusters of variant amino acids which may contribute to buried B cell epitopes, on all VSG molecules. Interestingly, this analysis also revealed a VSG consensus sequence in which certain conserved motifs are present in all VSGs. The shared elements of VSG sequences corresponded to known secondary structures present in MiTat 1.2, and included groups of conserved amino acids responsible for turns in subregions of the protein, for structural positioning of the variable residues on the exposed surface, and for the dimerization of VSG monomers. Overall, these observations may aid in the targeting and mapping of exposed and buried VSG specific B cell epitopes, and also may offer clues as to elements of the primary sequence that are important for the conserved 3-dimensional structure of antigenically distinct VSG molecules.
锥虫可变表面糖蛋白（VSG）上B细胞表位的特征取决于对可变特异性氨基酸序列的阐明，这些序列可能由于这些分子在表面被膜中的天然构象而暴露或埋藏。尽管不同的VSG具有异质的一级序列和独特的抗原特性，但最近对VSG的高分辨率X射线晶体学分析揭示了这些表面蛋白共有的保守三维结构[19]。我们利用这种保守的结构构象来帮助预测VSG分子的哪些可变亚区域可能包含暴露或埋藏的可变特异性B细胞表位。使用Staden数据表，我们将在本实验室中已进行免疫学特征分析的布氏罗得西亚锥虫LouTat 1 VSG的推导氨基酸序列与其他12个完整的VSG序列进行了比对，包括在晶体学研究中已进行特征分析的布氏布氏锥虫MiTat 1.2 VSG。该分析结果预测，在所有VSG分子上，有八个确定的可变氨基酸簇可能有助于暴露的B细胞表位，还有十个确定的可变氨基酸簇可能有助于埋藏的B细胞表位。有趣的是，该分析还揭示了一个VSG共有序列，其中某些保守基序存在于所有VSG中。VSG序列的共享元件对应于MiTat 1.2中存在的已知二级结构，包括负责蛋白质亚区域中转折、负责可变残基在暴露表面上的结构定位以及负责VSG单体二聚化的保守氨基酸组。总体而言，这些观察结果可能有助于对暴露和埋藏的VSG特异性B细胞表位进行靶向和定位，也可能为对于抗原性不同的VSG分子的保守三维结构重要的一级序列元件提供线索。
