Abstract

As part of an international effort to develop vaccines for Theileria lestoquardi, we undertook a limited screen to test T. lestoquardi orthologues of antigens recognised by CD8+ T lymphocyte responses against T. annulata and T. parva in cattle. Five MHC defined sheep were immunized by live T. lestoquardi infection and their CD8+ T lymphocyte responses determined. Thirteen T. lestoquardi orthologues of T. parva and T. annulata genes, previously shown to be targets of CD8+ T lymphocyte responses of immune cattle, were expressed in autologous fibroblasts and screened for T cell recognition using an IFNγ assay. Genes encoding T. lestoquardi antigens Tl8 (putative cysteine proteinase, 349 aa) or Tl9 (hypothetical secreted protein, 293 aa) were recognise by T cells from one animal that displayed a unique MHC class I genotype. Antigenic 9-mer peptide epitopes of Tl8 and Tl9 were identified through peptide scans using CD8+ T cells from the responding animal. These experiments identify the first T. lestoquardi antigens recognised by CD8+ T cell responses linked to specific MHC class I alleles.

Highlights

  • Theileria species are tick-transmitted hemoprotozoan parasites infecting wild and domestic ungulates in many areas of the world

  • Based on genetic and pathogenic similarities of T. lestoquardi to T. annulata and T. parva, we propose that similar responses are likely to be involved in immunity against T. lestoquardi and that recognition of immunodominant T cell antigens orthologous to those of T. annulata/ T. parva may occur

  • A subunit vaccine against T. lestoquardi is an attractive alternative strategy to live attenuated vaccines; there is limited available data on T. lestoquardi antigens and the immune responses against them. This is the first report of CD8+ T cells from immunized sheep having cytotoxic activity against T. lestoquardi-infected lymphocytes and identification of potential T. lestoquardi antigens that can be recognised by this CD8+ T cell response

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Summary

Introduction

Theileria species are tick-transmitted hemoprotozoan parasites infecting wild and domestic ungulates in many areas of the world. The most economically important species are T. parva and T. annulata, which are pathogenic to cattle, and T. lestoquardi (formerly T. hirci), which is pathogenic to sheep. Sheep are valuable commodities in North Africa, Asia, and the Middle East, and there is a need for better prevention and/or treatment measures in order to reduce the economic burden of disease caused by T. lestoquardi. Infection with T. lestoquardi causes an acute disease known as malignant ovine theileriosis. Clinical signs include loss of condition, coughing, lethargy, enlargement of lymph nodes, and PLOS ONE | DOI:10.1371/journal.pone.0162571. Clinical signs include loss of condition, coughing, lethargy, enlargement of lymph nodes, and PLOS ONE | DOI:10.1371/journal.pone.0162571 September 9, 2016

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