Hall T M, Joseph G T, Strand M
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Exp Parasitol. 1995 Mar;80(2):242-9. doi: 10.1006/expr.1995.1030.
Praziquantel is the drug of choice for human schistosomiasis. The efficacy of this drug is impaired in immune-deficient mice. However, transfer to B cell-depleted mice of a monoclonal antibody that recognizes a 200-kDa GPI-anchored glycoprotein of S. mansoni restores the effectiveness of praziquantel. In order to characterize this target antigen, we have isolated and sequenced cDNA clones encoding the 200-kDa protein. Three overlapping cDNA clones contained the complete nucleotide sequence. The sequences of five tryptic peptides from the native 200-kDa protein could be matched with regions in the amino acid sequence deduced from the nucleotide sequence of the isolated clones. This deduced amino acid sequence differed from sequences available in six databases. Praziquantel exposes epitopes on the worm surface that are normally not exposed, and we have shown by immunofluorescent staining that the fusion protein encoded by one of our cDNA clones expresses epitopes that are exposed on the surface of praziquantel-treated worms.
吡喹酮是治疗人类血吸虫病的首选药物。在免疫缺陷小鼠中，这种药物的疗效会受到损害。然而，将一种识别曼氏血吸虫200 kDa糖基磷脂酰肌醇（GPI）锚定糖蛋白的单克隆抗体转移到B细胞缺失的小鼠中，可恢复吡喹酮的有效性。为了鉴定这种靶抗原，我们分离并测序了编码200 kDa蛋白的cDNA克隆。三个重叠的cDNA克隆包含完整的核苷酸序列。来自天然200 kDa蛋白的五个胰蛋白酶肽段的序列可与从分离克隆的核苷酸序列推导的氨基酸序列区域相匹配。这种推导的氨基酸序列与六个数据库中可用的序列不同。吡喹酮可暴露蠕虫表面通常不暴露的表位，并且我们通过免疫荧光染色表明，我们的一个cDNA克隆编码的融合蛋白表达在吡喹酮处理的蠕虫表面暴露的表位。
