Two Theileria parva CD8 T Cell Antigen Genes Are More Variable in Buffalo than Cattle Parasites, but Differ in Pattern of Sequence Diversity

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.

Escape from CD8+ T Cell Response by Natural Variants of an Immunodominant Epitope from Theileria parva Is Predominantly Due to Loss of TCR Recognition

“…This is consistent with Tp1 and Tp2 sequencing data from laboratory-maintained parasite isolates, which have shown that sequences remain identical following tick passage of the parasites (R. Pelle, unpublished observations). Recent analyses of Tp2 nucleotide sequences have revealed evidence of positive selection at the codon level over the length of the gene, but the failure to detect obvious enrichment for positively selected residues within six defined epitopes compared with the remainder of the sequence suggested that the changes may not be due to immune selection (34). However, immune selection may not be detectable by this approach if the Tp2 protein contains a large number of additional undefined CD8 + T cell epitopes.…”

“…Moreover, recent analyses of field isolates of T. parva confirmed that both of these epitopes are polymorphic. The Tp2 Ag was found to be particularly variable, exhibiting substitutions in .70% of the amino acid residues, resulting in 23 allelic variants of the dominant A10-restricted epitope (Tp2 [49][50][51][52][53][54][55][56][57][58][59] ) among the 80 sequences examined (34). This unique set of naturally occurring parasite epitope variants provides a useful resource both to dissect the basis of strain specificity of the CD8 + T cell response and to investigate potential selective forces in generating polymorphism.…”

“…The recent identification of a large number of allelic variants of the Tp2 [49][50][51][52][53][54][55][56][57][58][59] epitope in field isolates of T. parva (34) provided an opportunity to analyze how polymorphism in the epitope influences T cell recognition and strain specificity of the T cell response.…”

Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review)

“…The Naegleria DNA still practices such transformations of its host (617,618). Later, in the unicellular parasite Theileria under immunological attack in an invaded bovine host, the most versatile theileria DNA encodes an elaborate physiology for the parasite to evade that immunological attack from its host (619). In the theileriainduced fatal lymphoproliferative disease, the East Coast fever, the parasite induces NFκB to secure apoptosisfree state of the schizontinfected lymphocytes.…”

High-resolution genotyping and mapping of recombination and gene conversion in the protozoan Theileria parva using whole genome sequencing

“…In-depth studies for T. parva are at an early stage due to lack of informative high-resolution markers. The approaches previously used to dissect T. parva parasite polymorphism and recombination events include monoclonal antibodies [9], gene probes binding to multi-copy loci [5], panels of micro- and mini-satellite markers [10,11] and most recently the sequence polymorphism in antigens that are targets of CD8+ T cell responses [12]. While useful to generate preliminary information, these techniques were unable to provide high resolution dissection of recombination events at the whole genome level.…”