Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis
The discovery of novel antigens is an essential requirement in devising new diagnostics or vaccines for use in control programmes against human tuberculosis (TB) and bovine tuberculosis (bTB). Identification of potential epitopes recognised by CD4+ T cells requires prediction of peptide binding to M...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Microbiology Society
2016
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| _version_ | 1826281957784289280 |
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| author | Farrell, D Jones, G Pirson, C Malone, K Rue-Albrecht, K Chubb, A Vordermeier, M Gordon, S |
| author_facet | Farrell, D Jones, G Pirson, C Malone, K Rue-Albrecht, K Chubb, A Vordermeier, M Gordon, S |
| author_sort | Farrell, D |
| collection | OXFORD |
| description | The discovery of novel antigens is an essential requirement in devising new diagnostics or vaccines for use in control programmes against human tuberculosis (TB) and bovine tuberculosis (bTB). Identification of potential epitopes recognised by CD4+ T cells requires prediction of peptide binding to MHC class-II, an obligatory prerequisite for T cell recognition. To comprehensively prioritise potential MHC-II-binding epitopes from Mycobacterium bovis, the agent of bTB and zoonotic TB in humans, we integrated three binding prediction methods with the M. bovisproteome using a subset of human HLA alleles to approximate the binding of epitope-containing peptides to the bovine MHC class II molecule BoLA-DRB3. Two parallel strategies were then applied to filter the resulting set of binders: identification of the top-scoring binders or clusters of binders. Our approach was tested experimentally by assessing the capacity of predicted promiscuous peptides to drive interferon-γ secretion from T cells of M. bovis infected cattle. Thus, 376 20-mer peptides, were synthesised (270 predicted epitopes, 94 random peptides with low predictive scores and 12 positive controls of known epitopes). The results of this validation demonstrated significant enrichment (>24 %) of promiscuously recognised peptides predicted in our selection strategies, compared with randomly selected peptides with low prediction scores. Our strategy offers a general approach to the identification of promiscuous epitopes tailored to target populations where there is limited knowledge of MHC allelic diversity. |
| first_indexed | 2024-03-07T00:36:38Z |
| format | Journal article |
| id | oxford-uuid:81a4e374-5b51-4f25-9774-8ea86e3ba1a1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:36:38Z |
| publishDate | 2016 |
| publisher | Microbiology Society |
| record_format | dspace |
| spelling | oxford-uuid:81a4e374-5b51-4f25-9774-8ea86e3ba1a12022-03-26T21:31:38ZIntegrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:81a4e374-5b51-4f25-9774-8ea86e3ba1a1EnglishSymplectic Elements at OxfordMicrobiology Society2016Farrell, DJones, GPirson, CMalone, KRue-Albrecht, KChubb, AVordermeier, MGordon, SThe discovery of novel antigens is an essential requirement in devising new diagnostics or vaccines for use in control programmes against human tuberculosis (TB) and bovine tuberculosis (bTB). Identification of potential epitopes recognised by CD4+ T cells requires prediction of peptide binding to MHC class-II, an obligatory prerequisite for T cell recognition. To comprehensively prioritise potential MHC-II-binding epitopes from Mycobacterium bovis, the agent of bTB and zoonotic TB in humans, we integrated three binding prediction methods with the M. bovisproteome using a subset of human HLA alleles to approximate the binding of epitope-containing peptides to the bovine MHC class II molecule BoLA-DRB3. Two parallel strategies were then applied to filter the resulting set of binders: identification of the top-scoring binders or clusters of binders. Our approach was tested experimentally by assessing the capacity of predicted promiscuous peptides to drive interferon-γ secretion from T cells of M. bovis infected cattle. Thus, 376 20-mer peptides, were synthesised (270 predicted epitopes, 94 random peptides with low predictive scores and 12 positive controls of known epitopes). The results of this validation demonstrated significant enrichment (>24 %) of promiscuously recognised peptides predicted in our selection strategies, compared with randomly selected peptides with low prediction scores. Our strategy offers a general approach to the identification of promiscuous epitopes tailored to target populations where there is limited knowledge of MHC allelic diversity. |
| spellingShingle | Farrell, D Jones, G Pirson, C Malone, K Rue-Albrecht, K Chubb, A Vordermeier, M Gordon, S Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis |
| title | Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis |
| title_full | Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis |
| title_fullStr | Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis |
| title_full_unstemmed | Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis |
| title_short | Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis |
| title_sort | integrated computational prediction and experimental validation identifies promiscuous t cell epitopes in the proteome of mycobacterium bovis |
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