CD8 T‐cell responses against the immunodominant Theileria parva peptide Tp249–59 are composed of two distinct populations specific for overlapping 11‐mer and 10‐mer epitopes
نویسندگان
چکیده
Immunity against Theileria parva is associated with CD8 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 Tp249-59 and Tp1214-224 epitopes dominate CD8 T-cell responses in BoLA-A10 and BoLA-18 MHC I homozygous animals, respectively. In this study, peptide-MHC I tetramers for these epitopes, and a subdominant BoLA-A10-restricted epitope (Tp298-106 ), were generated to facilitate accurate and rapid enumeration of epitope-specific CD8 T cells. During validation of these tetramers a substantial proportion of Tp249-59 -reactive T cells failed to bind the tetramer, suggesting that this population was heterogeneous with respect to the recognized epitope. We demonstrate that Tp250-59 represents a distinct epitope and that tetramers produced with Tp50-59 and Tp49-59 show no cross-reactivity. The Tp249-59 and Tp250-59 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 Tcell receptor β sequence analysis showed that Tp249-59 and Tp250-59 are recognized by non-overlapping T-cell receptor repertoires. Together these data demonstrate that although differing by only a single residue, Tp249-59 and Tp250-59 epitopes form distinct ligands for T-cell receptor recognition. Tetramer analysis of T. parva-specific CD8 T-cell lines confirmed the immunodominance of Tp1214-224 in BoLA-A18 animals and showed in BoLA-A10 animals that the Tp249-59 epitope response was generally more dominant than the Tp250-59 response and confirmed that the Tp298-106 response was subdominant.
منابع مشابه
Identification of Mycobacterium tuberculosis CTL Epitopes Restricted by HLA-A*0201 in HHD Mice
CD8+ T cells are thought to play an important role in protective immunity to tuberculosis. The major histocompatibility complex class I subtype HLA-A*0201 is one of the most prevalent class I alleles, with a frequency of over 30% in most populations. HLA-A*0201 transgenic, H-2Db/mouse beta2-microglobulin double-knockout mice (HHD) which express human HLA-A*0201 but no mouse class I, was shown t...
متن کاملشناسایی اپی توپهای سلولهای CD4+ T در پروتئین ترشحی MPB51 مایکوباکتریوم توبرکلوزیس در موشهای C57BL/6
Introduction & Objective: Both CD4+ type 1 helper (Th1) cells and CD8+ T cells play effective roles in protection against Mycobacterium tuberculosis infection. DNA vaccine encoding MPB51 can induce Th1-type immune responses and protective immunity upon challenge with M.tuberculosis. This study address to identify T-cell immunodominant epitopes on MPB51 in C57BL/6 mice. Materials & Methods : ...
متن کاملEscape from CD8+ T cell response by natural variants of an immunodominant epitope from Theileria parva is predominantly due to loss of TCR recognition.
Polymorphism of immunodominant CD8(+) T cell epitopes can facilitate escape from immune recognition of pathogens, leading to strain-specific immunity. In this study, we examined the TCR β-chain (TRB) diversity of the CD8(+) T cell responses of cattle against two immunodominant epitopes from Theileria parva (Tp1(214-224) and Tp2(49-59)) and investigated the role of TCR recognition and MHC bindin...
متن کاملIdentification of Theileria lestoquardi Antigens Recognized by CD8+ T Cells
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 ortholo...
متن کاملLinear peptide specificity of bovine antibody responses to p67 of Theileria parva and sequence diversity of sporozoite-neutralizing epitopes: implications for a vaccine.
A stage-specific surface antigen of Theileria parva, p67, is the basis for the development of an anti-sporozoite vaccine for the control of East Coast fever (ECF) in cattle. By Pepscan analysis with a series of overlapping synthetic p67 peptides, the antigen was shown to contain five distinct linear peptide sequences recognized by sporozoite-neutralizing murine monoclonal antibodies. Three epit...
متن کامل