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- W2514276035 abstract "Immunity against Theileria parva is associated with CD8 T-cell responsesthat exhibit immunodominance, focusing the response against limitednumbers of epitopes. As candidates for inclusion in vaccines, characterizationof responses against immunodominant epitopes is a key componentin novel vaccine development. We have previously demonstrated that theTp249–59 and Tp1214–224 epitopes dominate CD8 T-cell responses in BoLAA10and BoLA-18 MHC I homozygous animals, respectively. In thisstudy, peptide–MHC I tetramers for these epitopes, and a subdominantBoLA-A10-restricted epitope (Tp298–106), were generated to facilitate accurateand rapid enumeration of epitope-specific CD8 T cells. During validationof these tetramers a substantial proportion of Tp249–59-reactive Tcells failed to bind the tetramer, suggesting that this population washeterogeneous with respect to the recognized epitope. We demonstratethat Tp250–59 represents a distinct epitope and that tetramers producedwith Tp50–59 and Tp49–59 show no cross-reactivity. The Tp249–59 andTp250–59 epitopes use different serine residues as the N-terminal anchorfor binding to the presenting MHC I molecule. Molecular dynamic modellingpredicts that the two peptide–MHC I complexes adopt structurallydifferent conformations and Tcell receptor b sequence analysis showedthat Tp249–59 and Tp250–59 are recognized by non-overlapping T-cellreceptor repertoires. Together these data demonstrate that although differingby only a single residue, Tp249–59 and Tp250–59 epitopes form distinctligands for T-cell receptor recognition. Tetramer analysis of T. parva-specificCD8 T-cell lines confirmed the immunodominance of Tp1214–224 inBoLA-A18 animals and showed in BoLA-A10 animals that the Tp249–59epitope response was generally more dominant than the Tp250–59 responseand confirmed that the Tp298–106 response was subdominant." @default.
- W2514276035 created "2016-09-16" @default.
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- W2514276035 date "2016-06-01" @default.
- W2514276035 modified "2023-09-26" @default.
- W2514276035 title "CD8 T cell responses against the immunodominant Theileria parva 1 peptide Tp249-59 are composed of two distinct populations specific for 2 overlapping 11-mer and 10-mer epitopes 3 Short title: Overlapping 11- and 10-mer CD8+ T cell epitopes in Tp2. 4" @default.
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