Schistosoma mansoni: molecular cloning and sequencing of the 200-kDa chemotherapeutic target antigen.
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.
Hall
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TM
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Joseph
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GT
Strand
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D000595:Amino Acid Sequence; D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D000947:Antigens, Helminth / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D015152:Blotting, Northern; D018509:DNA, Helminth / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007106:Immune Sera / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011223:Praziquantel / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012550:Schistosoma mansoni / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000276:immunology; D012984:Software
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D018509:DNA, Helminth; D000939:Epitopes; D007106:Immune Sera; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011223:Praziquantel