The immunogenicity of Echinococcus granulosus antigen 5 is determined by its post-translational modifications.
Since its early introduction as a marker for the immunodiagnosis of hydatid disease, antigen 5 (Ag5) has been regarded as one of the more relevant antigens of Echinococcus granulosus, and it is still widely used in different confirmation techniques. In this work we prepared 2 recombinant forms of the antigen, namely, rAg5 (corresponding to the unprocessed polypeptide chain of the antigen) and rAg5-38s (corresponding to its 38 kDa subunit). Their antigenicities were compared to that of the native antigen using a human serum collection. There was a major drop in the reactivity of the sera, particularly against rAg5-38s, which was confirmed by analysis of the cross-reactivity of 2 panels of monoclonal antibodies specific for rAg5-38s and the native antigen. Using the chemically deglycosylated native antigen, we demonstrated that the reduced antigenicity of the recombinants is due to the loss of the sugar determinants, and not to their misfolding. Inhibition experiments using phosphorylcholine confirmed that this moiety also contributes to the reactivity of the antigen, but to a much lesser extent. The presence of immunodominant highly cross-reactive glycan moieties in the Ag5 molecule may involve a parasite evasion mechanism.
Lorenzo
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Cátedra de Inmunología, Facultad de Química, UDELAR, Instituto de Higiene, Av. A. Navarro 3051, piso 2, 11600 Montevideo, Uruguay.
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González-Sapienza
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D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D004443:Echinococcosis / Q000276:immunology; D048209:Echinococcus granulosus / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006031:Glycosylation; D015801:Helminth Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D010767:Phosphorylcholine / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D000939:Epitopes; D015801:Helminth Proteins; D021122:Protein Subunits; D010767:Phosphorylcholine