Peptide mimotopes of Mycobacterium tuberculosis carbohydrate immunodeterminants
Peptide mimotopes of Mycobacterium tuberculosis carbohydrate immunodeterminants
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DOI：
10.1042/bj20041139
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发表时间：
2005-04-15
影响因子：
4.1
通讯作者：
López-Marín, LM
中科院分区：
文献类型：
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作者：
Gevorkian, G;Segura, E;López-Marín, LM
结核分枝杆菌细胞表面抗原是结核病致病性的重要因素，可作为结核病免疫诊断的有效抗原。在本研究中，我们报告了成功的抗原性和免疫原性的模拟含甘露糖的细胞壁化合物的M。通过噬菌体展示技术鉴定的十二聚体肽对结核杆菌的作用。用兔抗M.作为生物淘选的靶标，鉴定了具有三种不同共有序列的肽。噬菌体展示和化学合成的肽与抗碳水化合物抗血清结合。针对肽QEPLMGTVPIRAGGGS引发的兔抗体识别甘露糖基化的M。结核病细胞壁抗原阿拉伯甘露聚糖和脂阿拉伯甘露聚糖，以及糖基化重组蛋白丙氨酸/脯氨酸富集抗原。此外，抗体也能够与来自酿酒酵母的甘露聚糖反应，但不与来自分枝杆菌的磷脂酰肌醇二甘露糖苷或阿拉伯半乳聚糖反应。这些结果表明，免疫原性肽模拟寡甘露糖苷表位。有趣的是，这份报告提供的证据表明，在与以前已知的碳水化合物mimotopes相比，没有芳香族残基是必要的肽序列模仿不寻常的分枝杆菌合成的糖缀合物。确定的肽模拟表位作为替代试剂的免疫诊断和天然非肽表位的功能作用的研究的可能用途进行了讨论。
Cell-surface saccharides of Mycobacterium tuberculosis appear to be crucial factors in tuberculosis pathogenicity and could be useful antigens in tuberculosis immunodiagnosis. In the present study, we report the successful antigenic and immunogenic mimicry of mannose-containing cell-wall compounds of M. tuberculosis by dodecamer peptides identified by phage-display technology. Using a rabbit antiserum raised against M. tuberculosis cell-surface saccharides as a target for biopanning, peptides with three different consensus sequences were identified. Phage-displayed and chemically synthesized peptides bound to the anti-carbohydrate antiserum. Rabbit antibodies elicited against the peptide QEPLMGTVPIRAGGGS recognize the mannosylated M. tuberculosis cell-wall antigens arabinomannan and lipoarabinomannan, and the glycosylated recombinant protein alanine/proline-rich antigen. Furthermore, antibodies were also able to react with mannan from Saccharomyces cerevisiae but not with phosphatidylinositol dimannosides or arabinogalactan from mycobacteria. These results suggest that the immunogenic peptide mimics oligomannosidic epitopes. Interestingly, this report provides evidence that, in contrast with previously known carbohydrate mimotopes, no aromatic residues are necessary in a peptide sequence for mimicking unusual glycoconjugates synthesized by mycobacteria. The possible usefulness of the identified peptide mimotopes as surrogate reagents for immunodiagnosis and for the study of functional roles of the native non-peptide epitopes is discussed.