Identification of CD8 epitopes in cattle pathogens by systematic synergistic analysis of peptide specificity and 3D structures of cattle MHC class I. (360G-Wellcome-079287_Z_06_Z)

Research into the immune systems of cattle and other economically important species focuses on disease control. Vaccines which can protect cattle against important pathogens are often only partially effective as they often do not generate a cellular immune response. Thus there is an increasing effort to determine MHC restricted T cell epitopes. Of farm livestock, cattle MHC has been relatively well-characterised, although at the molecular/genome level, this is still some way behind human or mous e MHC. Immunoinformatic epitope prediction tools allow us to use the wealth of pathogen genomes now available without the need for labour-intensive, time-consuming, and expensive large-scale in vitro assays. Our objective is to develop in silico tools which can accelerate cattle vaccine discovery through the rapid identification of epitopes. 1. To obtain crystal structures for at least two cattle MHC class I molecules, each bound to one or more self or pathogen-derived peptides. 2. To gene rate detailed peptide binding data for at least two cattle MHC class I molecules using several in vitro binding assays. 3. To develop robust in silico prediction methods using data generated in 1 and 2. 4. To verify our predictions using bovine TB, RSV and FMDV functional in vitro assays.