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CD 8 T‐cell responses against the immunodominant Theileria parva peptide Tp2 49–59 are composed of two distinct populations specific for overlapping 11‐mer and 10‐mer epitopes
Author(s) -
Connelley Timothy K.,
Li Xiaoying,
MacHugh Niall,
Colau Didier,
Graham Simon P.,
Bruggen Pierre,
Taracha Evans L.,
Gill Andy,
Morrison William Ivan
Publication year - 2016
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12637
Subject(s) - epitope , immunodominance , subdominant , biology , theileria parva , t cell , major histocompatibility complex , antigen , microbiology and biotechnology , population , virology , chemistry , immune system , immunology , medicine , parasite hosting , environmental health , world wide web , computer science
Summary Immunity against Theileria parva is associated with CD 8 T‐cell responses that exhibit immunodominance, focusing the response against limited numbers of epitopes. As candidates for inclusion in vaccines, characterization of responses against immunodominant epitopes is a key component in novel vaccine development. We have previously demonstrated that the Tp2 49–59 and Tp1 214–224 epitopes dominate CD 8 T‐cell responses in Bo LA ‐A10 and Bo LA ‐18 MHC I homozygous animals, respectively. In this study, peptide– MHC I tetramers for these epitopes, and a subdominant Bo LA ‐A10‐restricted epitope (Tp2 98–106 ), were generated to facilitate accurate and rapid enumeration of epitope‐specific CD 8 T cells. During validation of these tetramers a substantial proportion of Tp2 49–59 ‐reactive T cells failed to bind the tetramer, suggesting that this population was heterogeneous with respect to the recognized epitope. We demonstrate that Tp2 50–59 represents a distinct epitope and that tetramers produced with Tp 50–59 and Tp 49–59 show no cross‐reactivity. The Tp2 49–59 and Tp2 50–59 epitopes use different serine residues as the N‐terminal anchor for binding to the presenting MHC I molecule. Molecular dynamic modelling predicts that the two peptide– MHC I complexes adopt structurally different conformations and T cell receptor β sequence analysis showed that Tp2 49–59 and Tp2 50–59 are recognized by non‐overlapping T ‐cell receptor repertoires. Together these data demonstrate that although differing by only a single residue, Tp2 49–59 and Tp2 50–59 epitopes form distinct ligands for T ‐cell receptor recognition. Tetramer analysis of T. parva ‐specific CD 8 T‐cell lines confirmed the immunodominance of Tp1 214–224 in Bo LA ‐A18 animals and showed in Bo LA ‐A10 animals that the Tp2 49–59 epitope response was generally more dominant than the Tp2 50–59 response and confirmed that the Tp2 98–106 response was subdominant.