The bovine cytotoxic T cell: MHC restriction and antigen-specificity

The analysis of the immune mechanisms operative against the bovine intracellular protozoan parasite Theileria parva resulted in the identification and characterisation of the bovine cytotoxic T lymphocyte (CTL) and its important role in protection against this parasite. By the use of polyclonal and monoclonal antibodies specific for bovine MHC antigens and lymphocyte populations and the use of MHC-haplotyped animals it was possible to demonstrate the MHC restriction and antigen-specificity of the Theileria-specific cytotoxicity. In cross-protection studies with different parasite stocks or strains, a consistent correlation could be observed between the strain specificity of the CTL and the in vivo cross-protection. Moreover, the in vitro generation of CTL lines and clones and the development of a standardised technique for analysing the frequency of parasite-specific CTL precursors in cattle immunised with Theileria parva, enabled the identification of parameters influencing the parasite strain specificity of the cytotoxic response. Not only the immunising parasite but also the bovine MHC haplotype of the respective immunised animal influenced whether the Theileria-specific CTL were strain-specific or cross-reactive between strains. These results have important implications for the identification of cross-reactive CTL epitopes of the parasite in the development of subunit vaccines for outbred animals.