Reference | ||
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Reference Type | Literature | IEDB_Reference:1001089 |
Title | Antigen mining with iterative genome screens identifies novel diagnostics for the Mycobacterium tuberculosis complex. | |
Authors | Katie Ewer; Paul Cockle; Steve Gordon; Huma Mansoor; Marc Govaerts; Karl Walravens; Sylvie Marché; Glyn Hewinson; Martin Vordermeier | |
Affiliations | TB Research Group, Veterinary Laboratories Agency-Weybridge, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom. k.ewer@vla.defra.gsi.gov.uk. | |
Journal | Clin Vaccine Immunol | |
Year | 2006 | |
Abstract | The definition of antigens for the diagnosis of human and bovine tuberculosis is a research priority. If diagnosis is to be used alongside Mycobacterium bovis BCG-based vaccination regimens, it will be necessary to have reagents that allow the discrimination of infected and vaccinated animals. A list of 42 potential M. bovis-specific antigens was prepared by comparative analysis of the genomes of M. bovis, M. avium subsp. avium, M. avium subsp. paratuberculosis, and Streptomyces coelicolor. Potential antigens were tested by applying them in a high-throughput peptide-based screening system to M. bovis-infected and BCG-vaccinated cattle and to cattle without prior exposure to M. bovis. A response hierarchy of antigens was established by comparing responses in infected animals. Three antigens (Mb2555, Mb2890, and Mb3895) were selected for further study, as they were strongly recognized in experimentally infected animals but with low or no frequency in BCG-vaccinated and naïve cows. Interestingly, all three antigens were recognized in animals vaccinated against Johne's disease, suggesting the presences of epitopes cross-reacting with M. avium subsp. paratuberculosis antigens. Eight peptides from the three antigens studied in detail were identified as immunodominant and were characterized in terms of major histocompatibility complex class II restriction element usage and shown to be restricted through both DR and DQ molecules. Reasons for antigenic cross-reactivity with M. avium subsp. paratuberculosis and refinement of the in silico strategy to predict such cross-reactivity from the primary protein sequence will be discussed. Evaluation of the peptides identified from the three dominant antigens by use of larger field studies is now a priority. | |
Curation Last Updated | 2023-08-18 20:09:54 |
Epitope | ||
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Epitope ID | 11989 | IEDB_epitope:11989 |
Chemical Type | Linear peptide | |
Linear Sequence | EFETTRSSTGTGLQGVTSGL | |
Source Molecule Name | hypothetical protein Mb3895 | |
Source Organism | Mycobacterium tuberculosis variant bovis AF2122/97 | |
Starting Position | 57 | |
Ending Position | 76 |
Epitope Reference Details | ||
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Epitope Structure Defines | Epitope containing region/antigenic site | |
Epitope Name | Mb3895 p57-76 | |
Reference Starting Position | 57 | |
Reference Ending Position | 76 | |
Comments | This peptide epitope was selected from a panel of 20mer overlapping peptides representing the entire length of the conserved hypothetical protein identified by an iterative genome screen of Mycobacterium bovis using StandAlone TBLASTIN (NCBI). | |
Location of Data in Reference | Author provided |
Immunization | ||
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Host Organism | Bos taurus (bovine) |
1st In Vivo Process | ||
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In Vivo Process Type | Administration in vivo | |
Disease State | tuberculosis | |
Disease Stage | Acute/Recent onset; | OGMS:0000094 |
Administration Details | ||
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Route | intratracheal |
1st Immunogen | ||
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Epitope Relation | Source Organism | |
Object Type | Organism | |
Organism | Mycobacterium tuberculosis variant bovis AF2122/97 |
Immunogen Details | ||
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Immunogen Reference Name | Mycobacterium bovis AF2122/97 |
Immunization Comments | ||
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Immunization Comments | Eleven calves were previously exposed by natural infection with M. bovis in the field. Twenty-one calves from BTB-free herds were also immunized by experimental infection with 1-1000 CFUs of M. bovis (AF2122/97). Active bovine TB was confirmed by skin test, bacterial culture and postmortem pathology. Blood was collected 18 weeks post-infection. |
T Cell Assay | ||
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Qualitative Measurement | Positive | |
Method/Technique | ELISA | |
Measurement of | IFNg release |
Effector Cells | ||
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Effector Cell Tissue Type | Blood | |
Effector Cell Type | PBMC | |
Effector Cell Culture Conditions | Direct Ex Vivo |
Antigen Presenting Cells | ||
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Cell Tissue Type | Blood | |
Cell Type | PBMC | |
Cell Culture Conditions | Direct Ex Vivo |
Antigen | ||
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Epitope Relation | Epitope | |
Chemical Type | Linear peptide | |
Linear Sequence | EFETTRSSTGTGLQGVTSGL | |
Source Molecule Name | hypothetical protein Mb3895 | |
Source Organism | Mycobacterium tuberculosis variant bovis AF2122/97 | |
Starting Position | 57 | |
Ending Position | 76 |
Antigen Details | ||
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Antigen Reference Name | Mb3895 p57-76 |
Assay Reference Details | ||
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Assay Comments by IEDB Curator | The ability of individual Mb3895 peptides to induce IFNg production from the PBMCs of cattle infected with M. bovis was evaluated using ELISA. By comparison to the other peptides, this peptide was capable of inducing only low levels of IFNg. | |
Location of Assay Data in Reference | Figure 2 |