Location: Animal Disease Research
Project Number: 2090-32000-034-10-S
Project Type: Specific Cooperative Agreement
Start Date: Jul 7, 2014
End Date: Jun 30, 2017
Test the hypothesis that immunization with both CD4+ and CD8+ T-cell target antigens will induce a significantly greater memory CTL response to T. parva than immunization with CD8+ T-cell target antigens alone.
Significant MHC class II-restricted CD4+ helper T-cell responses to Theileria parva schizont-infected lymphocytes have also been demonstrated, but the role of helper T cells in the development of immunity to T. parva has not been fully elucidated. To date, thirteen schizont antigens targeted by CTLs have been identified, and five have been tested in immunization and challenge studies. In these studies, only 30% of immunized cattle exhibited a protective CTL response during subsequent T. parva challenge. Although two of the CTL target antigens also contain CD4+ T-cell epitopes, CD4+ T-cell responses to challenge were minimal. In vitro cytotoxicity studies indicate that priming of naive CD8+ T cells specific for T. parva- infected lymphocytes requires close contact with antigen-specific CD4+ T cells. Furthermore, it is well established that CD4+ T-cell help is required to generate functional memory CTLs in most infectious and neoplastic diseases. Despite the documented importance of helper T cells in generating protective CTL responses in other infection models, only two T. parva schizont antigens targeted by CD4+ T cells have been identified. More complete characterization of the CD4+ T-cell target antigen repertoire will greatly accelerate the development of an efficacious T. parva subunit vaccine.