T cell mediated immunoregulation plays an important role in protective immunity. The central molecular interaction, which dictates the selection of the specificity of T cells, depends on the interaction between MHC molecules and peptides derived from degraded antigenic structures. Here, we studied this interaction between bovine MHC class II molecules and peptides derived from foot and mouth disease virus (FMDV). Progress during the last decade in our understanding of the mechanisms underlying antigen recognition by T lymphocytes, opens the possibility to apply this knowledge in new approaches for the development of vaccines. A competitive MHC-peptide binding assay on isolated bovine MHC class II DR molecules (BoLA-DR) was developed and used to study whether the selection of the defined T cell epitopes of FMDV in the context of three different BoLA class II haplotypes is mediated by DR molecules. Retro-inverso (RI) peptides, corresponding to the defined T cell epitopes of FMDV were analysed in their functional capacity to see if it is possible to induce a T cell response against these peptides and whether such a response might be cross-reactive with the natural epitope. Furthermore, in order to clarify in more detail the T cell assay results, their affinity to bind to the MHC class II molecules was studied by a competitive MHC-peptide binding assay. Furthermore, the structure based design was applied in order to define motifs for the three frequent bovine DRB3 (BoLA-DRB3) alleles. The biological activities of the motif were evaluated by MHC class II-peptide binding assay. Beside the development of a competitive MHC-peptide binding assay on isolated bovine MHC class II DR molecules (BoLA-DR), the selection of epitopes was shown to be a reflection of the restrictions defined by MHC class II molecules, and as a consequence the MHC dictates the epitope selection in a T cell response upon vaccination. However, it was clear that at the functional level, the RI-analogues were not useful cross-reactive epitopes at the T cell level. Peptide binding motifs for three frequent bovine DRB3 (BoLA-DRB3) alleles based on the molecular structure alone was also defined.

Keywords