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The bovine CD8+ T-cell response to Theileria parva displays epitope immunodominance and oligoclonality

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Title The bovine CD8+ T-cell response to Theileria parva displays epitope immunodominance and oligoclonality
 
Creator Connelley, T.
MacHugh, Niall D.
Graham, S.
Taracha, E.A.
Burrells, A.
Ngugi, D.
Morrison, W. Ivan
 
Subject THEILERIA PARVA
LYMPHOCYTES
BOVINAE
CLONES
 
Description Species: RuminantsTheileria parva is an intracellular protozoal parasite which causes East Coast Fever (ECF), a major constraint to cattle production in eastern and southern Africa. Characteristics of the protective CD8+ T-cell response against T. parva suggest it is focused on a limited number of immunodominant epitopes that exhibit polymorphism between parasite strains. The recent identification of antigens recognised by T. parva-specific CD8+ T-cells has created new opportunities in the development of a subunit vaccine, and permitted the specificity of the CD8+ response to be examined. Cyotoxicity assays with peptide-loaded targets, and analyses of TCRBV gene usage have been used to study the antigen specificity and clonal composition of the CD8+ memory population in T. parva immune animals. Analyses of large panels of T. parva-specific CD8+ T-cell clones from memory T-cells of immune animals homozygous for MHC haplotypes expressing either the A10 or A18 class I specificities, revealed that over 65% of the response was directed against a single immunodominant epitope (Tp1.1 for A18 and Tp2.2. for A10). TCRB-chain sequence analysis showed that for each immunodominant epitope the antigen-specific T-cells were polyclonal but dominated by large oligo-clonal expansions. These clonal expansions utilized different VB gene segments in different animals. Importantly, using a newly developed bovine TCRB-CDR3 heteroduplex assay, it has been possible to identify the same large T-cell clonal expansions in vivo following challenge with T. parva, indicating that the immunodominant populations of CD8+ T-cells observed in in vitro cultures are representative of the memory population present in vivo. This work provides the first definitive demonstration of immunodominance in a CD8+ T-cell response to a protozoan parasite, providing an explanation for the incomplete cross-protection between T. parva strains and has important implications for the design of a subunit vaccine.
 
Date 2009-10-28T05:19:33Z
2009-10-28T05:19:33Z
2009-03-15
 
Type Journal Article
 
Identifier Connelley, T.; Machugh,, N.; Graham, S.; Taracha,, E.; Burrells, A.; Ngugi, D.; Morrison, W.I. 2009. The bovine CD8+ T-cell response to Theileria parva displays epitope immunodominance and oligoclonality. Veterinary Immunology and Immunopathology (The Netherlands). v. 128(1-3). p. 288.
http://hdl.handle.net/10568/17
 
Language en
 
Source Veterinary Immunology and Immunopathology