T-cell mediated immunity and vaccine development in horses
The long-term goal of this research is to facilitate development of more effective vaccines against intracellular pathogens of the horse, such as equine herpesvirus type 1 (EHV-1), equine influenza (EIV), and Rhodococcus equi (R. equi). Vaccines for these microorganisms are not yet available or only partially effective. T-lymphocyte (T-cell) immunity is critical for protection against intracellular pathogens; however, details of the antigens recognized by T-cells and assays for measuring specific T-cell responses are not available for the horse. The T-cell receptor recognizes pathogen-derived peptides held in the binding groove of Major Histocompatibility Complex (MHC) molecules on the surface of infected cells. Our objective is to identify the immunogenic peptides bound by the most common equine MHC class I molecules. This information would advance the long-term goal of development of new diagnostic tools and improved vaccines.
Hypothesis
We propose that it is possible to identify immunogenic peptides recognized by equine T-cells through experiments that use genomic information from both host and pathogen.
Specific Aims:
1) To identify the most important MHC class I molecule that presents immunogenic peptide after EHV-1 infection in a common and well-studied horse MHC type;
2) To determine the amino acid sequence of the EHV-1 peptide bound by that MHC class I molecule;
3) To use the identified EHV-1 peptide sequence to predict peptides from other horse pathogens that bind to this MHC class I molecule.