Structural Analysis and Antibody Response to the Extracellular GlutathioneS-Transferases fromOnchocerca volvulus
| Autor: | Rolf D. Walter, Norbert W. Brattig, Harald S. Conradt, Eva Liebau, Peter Fischer, Alexandra Sommer, Manfred Nimtz, Kay Boettcher |
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| Rok vydání: | 2001 |
| Předmět: |
Models
Molecular Signal peptide Glycosylation Molecular Sequence Data Immunology Antibodies Helminth Oligosaccharides Protein Sorting Signals Onchocerciasis Microbiology Isozyme chemistry.chemical_compound Immune system Animals Humans Amino Acid Sequence Protein Precursors Glutathione Transferase Glycoproteins chemistry.chemical_classification biology Immunogenicity biology.organism_classification Onchocerca volvulus Isoenzymes Infectious Diseases Carbohydrate Sequence chemistry Biochemistry Antigens Helminth biology.protein Female Parasitology Fungal and Parasitic Infections Antibody Glycoprotein |
| Zdroj: | Infection and Immunity. 69:7718-7728 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.69.12.7718-7728.2001 |
| Popis: | Onchocerca volvulusis a human pathogenic filarial parasite which, like other parasitic nematodes, is capable of surviving in an immunologically competent host by employing a variety of immune evasion strategies and defense mechanisms including the detoxification and repair mechanisms of the glutathioneS-transferases (GSTs). In this study we analyzed the glycosylation pattern and the immunological properties of extracellularO. volvulusGST1a and -1b (OvGST1a and -1b). The enzymes differ in only 10 amino acids, and both are glycoproteins that have cleavable signal peptides and unusual N-terminal extensions. These characteristics have not been described for other GSTs so far. Mass spectrometry analyses indicate that both enzymes carry high-mannose type oligosaccharides on at least four glycosylation sites. Glycosylation sites 1 to 3 ofOvGST1a (OvGST1b sites 2 to 4) are occupied by truncated N-glycans (Man2GlcNAc2 to Man5GlcNAc2), and N glycosylation site 4 ofOvGST1a (OvGST1b site 5) carries Man5GlcNAc2 to Man9GlcNAc2. To analyze the capacity of these secretory GSTs to stimulate host immune responses, we studied the antibody responses of onchocerciasis patients against the native affinity-purifiedOvGST1a and -1b. By enzyme-linked immunosorbent assay we showed thatOvGST1a and -1b are immunodominant antigens, with less than 7% nonresponder patients. A direct comparison of the antibody responses to the glycosylated and deglycosylated forms demonstrates the high immunogenicity of the N-glycans. Analyses of the antibody responses to the unusual N-terminal extension show an enhanced recognition of this portion by patients as opposed to recognition of the recombinant protein without extension. |
| Databáze: | OpenAIRE |
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