Identification of Peptide Mimotopes of Trypanosoma brucei gambiense Variant Surface Glycoproteins
| Autor: | Tessa Dieltjens, Liesbeth Van Nieuwenhove, Yves Guisez, Philippe Büscher, Fatima Balharbi, Veerle Lejon, Stijn Rogé, Thierry Laurent |
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| Rok vydání: | 2011 |
| Předmět: |
Proteomics
Phage display Trypanosoma brucei gambiense Glycobiology Antibodies Protozoan Peptide Protozoology Biochemistry Epitope Epitopes Mice Sequencing African trypanosomiasis chemistry.chemical_classification biology lcsh:Public aspects of medicine Clinical Laboratory Sciences Infectious Diseases Monoclonal Medicine Sequence Analysis Variant Surface Glycoproteins Trypanosoma Research Article Trypanosoma lcsh:Arctic medicine. Tropical medicine lcsh:RC955-962 medicine.drug_class Immunology Immunoglobulins Trypanosoma brucei Monoclonal antibody Microbiology Diagnostic Medicine parasitic diseases medicine Synthetic Peptide Animals Humans Protein Interactions Biology Glycoproteins Immunity Public Health Environmental and Occupational Health lcsh:RA1-1270 biology.organism_classification medicine.disease Virology Molecular biology Trypanosomiasis African chemistry Humoral Immunity Parastic Protozoans Clinical Immunology Human medicine Peptides |
| Zdroj: | PLoS Neglected Tropical Diseases, Vol 5, Iss 6, p e1189 (2011) PLoS neglected tropical diseases PLoS Neglected Tropical Diseases |
| ISSN: | 1935-2735 1935-2727 |
| Popis: | Background The current antibody detection tests for the diagnosis of gambiense human African trypanosomiasis (HAT) are based on native variant surface glycoproteins (VSGs) of Trypanosoma brucei (T.b.) gambiense. These native VSGs are difficult to produce, and contain non-specific epitopes that may cause cross-reactions. We aimed to identify mimotopic peptides for epitopes of T.b. gambiense VSGs that, when produced synthetically, can replace the native proteins in antibody detection tests. Methodology/Principal Findings PhD.-12 and PhD.-C7C phage display peptide libraries were screened with mouse monoclonal antibodies against the predominant VSGs LiTat 1.3 and LiTat 1.5 of T.b. gambiense. Thirty seven different peptide sequences corresponding to a linear LiTat 1.5 VSG epitope and 17 sequences corresponding to a discontinuous LiTat 1.3 VSG epitope were identified. Seventeen of 22 synthetic peptides inhibited the binding of their homologous monoclonal to VSG LiTat 1.5 or LiTat 1.3. Binding of these monoclonal antibodies to respectively six and three synthetic mimotopic peptides of LiTat 1.5 and LiTat 1.3 was significantly inhibited by HAT sera (p Author Summary The control of human African trypanosomiasis or sleeping sickness, a deadly disease in sub-Saharan Africa, mainly depends on a correct diagnosis and treatment. The aim of our study was to identify mimotopic peptides (mimotopes) that may replace the native proteins in antibody detection tests for sleeping sickness and hereby improve the diagnostic sensitivity and specificity. We selected peptide expressing phages from the PhD.-12 and PhD.-C7C phage display libraries with mouse monoclonal antibodies specific to variant surface glycoprotein (VSG) LiTat 1.3 or LiTat 1.5 of Trypanosoma brucei gambiense. The peptide coding genes of the selected phages were sequenced and the corresponding peptides were synthesised. Several of the synthetic peptides were confirmed as mimotopes for VSG LiTat 1.3 or LiTat 1.5 since they were able to inhibit the binding of their homologous monoclonal to the corresponding VSG. These peptides were biotinylated and their diagnostic potential was assessed with human sera. We successfully demonstrated that human sleeping sickness sera recognise some of the mimotopes of VSG LiTat 1.3 and LiTat 1.5, indicating the diagnostic potential of such peptides. |
| Databáze: | OpenAIRE |
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