Abstract
Background Theileria parva causes an acute fatal disease in cattle, but infections are asymptomatic in the African buffalo (Syncerus caffer). Cattle can be immunized against the parasite by infection and treatment, but immunity is partially strain specific. Available data indicate that CD8+ T lymphocyte responses mediate protection and, recently, several parasite antigens recognised by CD8+ T cells have been identified. This study set out to determine the nature and extent of polymorphism in two of these antigens, Tp1 and Tp2, which contain defined CD8+ T-cell epitopes, and to analyse the sequences for evidence of selection.Methodology/Principal FindingsPartial sequencing of the Tp1 gene and the full-length Tp2 gene from 82 T. parva isolates revealed extensive polymorphism in both antigens, including the epitope-containing regions. Single nucleotide polymorphisms were detected at 51 positions (∼12%) in Tp1 and in 320 positions (∼61%) in Tp2. Together with two short indels in Tp1, these resulted in 30 and 42 protein variants of Tp1 and Tp2, respectively. Although evidence of positive selection was found for multiple amino acid residues, there was no preferential involvement of T cell epitope residues. Overall, the extent of diversity was much greater in T. parva isolates originating from buffalo than in isolates known to be transmissible among cattle.Conclusions/SignificanceThe results indicate that T. parva parasites maintained in cattle represent a subset of the overall T. parva population, which has become adapted for tick transmission between cattle. The absence of obvious enrichment for positively selected amino acid residues within defined epitopes indicates either that diversity is not predominantly driven by selection exerted by host T cells, or that such selection is not detectable by the methods employed due to unidentified epitopes elsewhere in the antigens. Further functional studies are required to address this latter point.
Highlights
Theileria parva is a tick-transmitted protozoan parasite that causes East Coast fever (ECF), an economically important disease of cattle in eastern, central and southern Africa
T. parva parasites that originate from buffalo are genotypically and antigenically closely related to T. parva maintained in cattle, available evidence indicates that a significant proportion of the buffalo-derived population cannot be transmitted between cattle
In order to determine the level of genetic diversity in isolates of T. parva obtained from cattle and buffalo in regions of Africa where ECF is endemic, sequence polymorphism analyses of two CD8 T cell target antigens, Tp1 and Tp2, were conducted
Summary
Theileria parva is a tick-transmitted protozoan parasite that causes East Coast fever (ECF), an economically important disease of cattle in eastern, central and southern Africa. The African buffalo (Syncerus caffer) is the natural reservoir of T. parva, but the parasite does not cause disease in this species. Transmission of buffalo-derived T. parva to cattle results in a rapidly lethal disease, but in many cases the parasites do not differentiate to the erythrocyte-infective stage and are not transmissible by ticks [6,7]. T. parva parasites that originate from buffalo are genotypically and antigenically closely related to T. parva maintained in cattle, available evidence indicates that a significant proportion of the buffalo-derived population cannot be transmitted between cattle. Theileria parva causes an acute fatal disease in cattle, but infections are asymptomatic in the African buffalo (Syncerus caffer). Available data indicate that CD8+ T lymphocyte responses mediate protection and, recently, several parasite antigens recognised by CD8+ T cells have been identified. This study set out to determine the nature and extent of polymorphism in two of these antigens, Tp1 and Tp2, which contain defined CD8+ T-cell epitopes, and to analyse the sequences for evidence of selection
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