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<jats:title>ABSTRACT</jats:title> <jats:p>The definition of antigens for the diagnosis of human and bovine tuberculosis is a research priority. If diagnosis is to be used alongside <jats:italic>Mycobacterium bovis</jats:italic> 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 <jats:italic>M. bovis-</jats:italic>specific antigens was prepared by comparative analysis of the genomes of <jats:italic>M. bovis</jats:italic>, <jats:italic>M. avium</jats:italic> subsp. <jats:italic>avium</jats:italic>, <jats:italic>M. avium</jats:italic> subsp. <jats:italic>paratuberculosis</jats:italic>, and <jats:italic>Streptomyces coelicolor</jats:italic>. Potential antigens were tested by applying them in a high-throughput peptide-based screening system to <jats:italic>M. bovis</jats:italic>-infected and BCG-vaccinated cattle and to cattle without prior exposure to <jats:italic>M. bovis</jats:italic>. 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 <jats:italic>M. avium</jats:italic> subsp. <jats:italic>paratuberculosis</jats:italic> 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 <jats:italic>M. avium</jats:italic> subsp. <jats:italic>paratuberculosis</jats:italic> 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.</jats:p>

Original publication

DOI

10.1128/cvi.13.1.90-97.2006

Type

Journal article

Journal

Clinical and Vaccine Immunology

Publisher

American Society for Microbiology

Publication Date

01/2006

Volume

13

Pages

90 - 97