Type

Journal Article

Authors

Stephen V. Gordon
Martin Vordermeier
Anthony J. Chubb
Kevin Rue-Albrecht
Kerri Malone
Christopher Pirson
Gareth Jones
Damien Farrell

Subjects

Veterinary

Topics
human bovine tuberculosis experimental t cell t cells peptide binding t cell recognition mycobacterium bovis bovine tuberculosis tb

Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis. (2016)

Abstract 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.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Stephen V. Gordon, Martin Vordermeier, Anthony J. Chubb, Kevin Rue-Albrecht, Kerri Malone, Christopher Pirson, Gareth Jones, Damien Farrell

Experts in our system

1
Stephen V. Gordon
University College Dublin
Total Publications: 40
 
2
Anthony J Chubb
Royal College of Surgeons in Ireland
Total Publications: 21
 
3
Kevin Rue-Albrecht
University College Dublin
Total Publications: 12
 
4
Kerri M. Malone
University College Dublin
Total Publications: 9
 
5
Damien Farrell
University College Dublin
Total Publications: 16