A GENERAL STRATEGY TO IDENTIFY MIMOTOPES OF PATHOLOGICAL ANTIGENS USING ONLY RANDOM PEPTIDE LIBRARIES AND HUMAN SERA
A GENERAL STRATEGY TO IDENTIFY MIMOTOPES OF PATHOLOGICAL ANTIGENS USING ONLY RANDOM PEPTIDE LIBRARIES AND HUMAN SERA
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DOI：
10.1002/j.1460-2075.1994.tb06501.x
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发表时间：
1994-05-01
期刊：
影响因子：
11.4
通讯作者：
NICOSIA, A
中科院分区：
文献类型：
--
作者：
FOLGORI, A;TAFI, R;NICOSIA, A
描述了一种利用人血清从噬菌体展示的随机肽库中鉴定疾病特异性表位的策略。通过亲和选择和噬菌斑的免疫学筛选，从> 10（7）个不同序列中纯化与患者血清中存在的抗体反应的噬菌体上的肽（噬菌体位）。疾病特异性吞噬表位可以通过仅利用患者和正常人血清的“抗原非依赖性”程序从该库中鉴定出来。使用这种策略，我们已经选择了两个不同的抗原表位的抗原模拟物（模拟表位），从人B病毒包膜蛋白（HBsAg）。我们可以表明，这些mimotopes的体液反应是广泛的免疫人群，这表明该战略确定吞噬抗原，具有潜在的诊断试剂的作用。用选定的吞噬表位免疫小鼠，引起针对HBsAg的强烈特异性应答。这些结果为疾病相关表位的发现开辟了新的途径，并为疫苗开发提供了潜力，而不需要使用病原体或其抗原，甚至不需要关于病原体或其抗原的信息。
A strategy to identify disease-specific epitopes from phage-displayed random peptide libraries using human sera is described. Peptides on phage (phagotopes) that react with antibodies present in patient sera are purified from > 10(7) different sequences by affinity selection and immunological screening of plaques. Disease-specific phagotopes can be identified out of this pool through an 'antigen independent' procedure which avails itself only of patient and normal human sera. Using this strategy, we have selected antigenic mimics (mimotopes) of two different epitopes from the human hepatitis B virus envelope protein (HBsAg). We could show that a humoral response to these mimotopes is widespread in the immunized population, suggesting that the strategy identifies phagotopes that have a potential role as diagnostic reagents. Immunization of mice with the selected phagotopes elicited a strong specific response against the HBsAg. These results open new inroads into disease-related epitope discovery and provide the potential for vaccine development without a requirement for the use of, or even information about, the aetiological agent or its antigens.