RECOGNITION BY HUMAN SERA AND IMMUNOGENICITY OF HBSAG MIMOTOPES SELECTED FROM AN M13 PHAGE DISPLAY LIBRARY

RECOGNITION BY HUMAN SERA AND IMMUNOGENICITY OF HBSAG MIMOTOPES SELECTED FROM AN M13 PHAGE DISPLAY LIBRARY
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DOI:
10.1016/0378-1119(94)90292-5
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发表时间:
1994-09-02
期刊:
影响因子:
3.5
通讯作者:
MONACI, P
MONACI, P
中科院分区:
生物学3区
文献类型:
--
作者:
MOTTI, C;NUZZO, M;MONACI, P

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我们使用两种对人乙型肝炎病毒表面抗原 (HBsAg) 具有特异性的小鼠单克隆抗体 (mAb) 来筛选包含 15 个氨基酸残基的随机肽库,该库显示为与丝状噬菌体 M13 的蛋白 III 的融合体。通过结合亲和力选择、免疫筛选和 ELISA 技术,我们选择了能被抗 HBsAg mAb 识别并与天然抗原具有相似性的肽。选定的噬菌体展示表位(噬菌体)表现为 HBsAg 的抗原模拟物。一种吞噬位可被 HBsAg 免疫个体的人血清特异性识别,表明可以使用吞噬位作为标记物来检测血清中特定抗体的存在。相同的吞噬位还在小鼠中引发针对 HBsAg 的抗体,表明 mAb 选择的吞噬位也可以是天然抗原的免疫原性模拟物。这些发现表明,有可能鉴定出可用作诊断试剂和开发无细胞疫苗的先导物的疾病特异性表位。
We used two mouse monoclonal antibodies (mAb) specific for the human hepatitis B virus surface antigen (HBsAg) to screen a random peptide library of 15 amino-acid residues displayed as a fusion to protein III of filamentous phage M13. By a combination of affinity selection, immune-screening and ELISA techniques, we selected peptides that are recognized by the anti-HBsAg mAb and show aa similarity with the natural antigen. The selected phage-displayed epitopes (phagotopes) behave as antigenic mimics of HBsAg. One phagotope is specifically recognized by human sera from HBsAg-immunized individuals, pointing to the possible use of phagotopes as markers to detect the presence of specific Ab in the serum. The same phagotope also elicits Ab directed against HBsAg in mice, indicating that mAb-selected phagotopes can also be immunogenic mimics of the natural antigen. These findings demonstrate that it is possible to identify disease-specific epitopes that can be used as diagnostic reagents and as leads for the development of acellular vaccines.