The pathogenic Theileria species Theileria parva and T. annulata infect bovine leukocytes and erythrocytes causing acute, often fatal lymphoproliferative diseases in cattle. The parasites are of interest not only because of their economic importance as pathogens, but also because of their unique ability to transform the leukocytes they infect. The latter property allows parasitized leukocytes to be cultured as continuously growing cell lines in vitro, thus providing an amenable in vitro system to study the parasite/host cell relationship and parasite-specific cellular immune responses. This paper summarizes important advances in knowledge of the immunobiology of these parasites over the last 40 years, focusing particularly on areas of relevance to vaccination.

Infections with Theileria parva in the African buffalo are invariably asymptomatic, whereas infections in cattle usually result in clinical disease, the severity of which varies in different populations of cattle. The parasite exhibits antigenic heterogeneity, which in cattle manifests as differences between parasite strains in their cross-protective properties. A series of studies on T cell responses to T. parva in cattle have demonstrated that class I MHC-restricted cytotoxic T lymphocytes (CTL), specific for parasitized lymphoblasts, are important mediators of immunity. Cytotoxic T cell responses frequently display parasite strain-restricted specificities which appear to correlate with the capacity of strains to cross-protect. The strain specificity of CTL responses varies in animals immunized with the same parasite strain and is influenced by both host and parasite genotype. Recent studies have provided evidence that there is competition between epitopes for induction of CTL responses, which can result in a bias to strain-specific epitopes. These properties of the CTL response have important implications for vaccination. Thus, in designing a vaccine, it may be possible, by selecting parasite proteins containing appropriate CTL epitopes, to generate CTL responses that protect against a wide range of parasite strains. Although there are no comparable data on CTL responses in the buffalo, it is considered that the features of the immune response described for cattle would be advantageous for survival of parasite populations in the buffalo. Specifically, a bias in the immune responses to strain-specific determinants should favour establishment of infection in buffalo already carrying the parasite and allow fluctuation in the levels of different parasite strains during the course of persistent infection.

The paper describes the development and analysis of a mathematical framework for the study of the within-host population dynamics of the interaction between macroparasites and the human immune system. Simple models of this interaction based on the proliferation of T cell clones specific to parasite antigen, and the impact of clonal expansion on parasite survival, capture the basic features of age-related changes in worm loads within human communities. The model is generalized to multiple epitopes on a single antigen, and reveals competitive exclusion amongst T cells, with a single clone becoming immunodominant in the absence of cross-reactive responses and genetic variation. The introduction of genetic heterogeneity and concomitant variability in the immunogenicity of specific epitopes induces additional complexity into the dynamical interaction. Most importantly, multiple epitope models with antigenic variation suggest that the immunodominant response may not necessarily be targeted at the epitope at which some strains show the greatest immunogenicity. High immunogenicity at a particular epitope can be masked by genetic variability even though many of the variants are more immunogenic at this epitope by comparison with the epitope to which the immunodominant immunological response is directed.