Systematic Determination of TCR–Antigen and Peptide–MHC Binding Kinetics among Field Variants of a Theileria parva Polymorphic CTL Epitope
Autor: | Svitek, Nicholas, Saya, Rosemary, Zhang, Houshuang, Nene, Vishvanath, Steinaa, Lucilla |
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Rok vydání: | 2022 |
Předmět: |
Immunity
Cellular Histocompatibility Antigens Class I Immunology Receptors Antigen T-Cell Cattle Diseases Epitopes T-Lymphocyte hemic and immune systems chemical and pharmacologic phenomena Antigens Protozoan Theileria parva Cell Line Theileriasis Antigen Recognition and Responses Animals Immunology and Allergy Cattle Amino Acid Sequence T-Lymphocytes Cytotoxic |
Zdroj: | The Journal of Immunology Author Choice |
ISSN: | 1550-6606 0022-1767 |
Popis: | Key Points Positions 1–3 in the Tp9 CTL epitope are required for binding to BoLA-1*023:01.Positions 5–8 in the Tp9 epitope are required for TCR recognition in diverse CTLs.Tp9-specific CTLs from Muguga-immunized animals can cross-react with variants 4 and 7. CTLs are known to contribute to immunity toward Theileria parva, the causative agent of East Coast fever. The Tp967–75 CTL epitope from the Muguga strain of T. parva is polymorphic in other parasite strains. Identifying the amino acids important for MHC class I binding, as well as TCR recognition of epitopes, can allow the strategic selection of Ags to induce cellular immunity toward T. parva. In this study, we characterized the amino acids important for MHC class I binding and TCR recognition in the Tp967–75 epitope using alanine scanning and a series of variant peptide sequences to probe these interactions. In a peptide–MHC class I binding assay, we found that the amino acids at positions 1, 2, and 3 were critical for binding to its restricting MHC class I molecule BoLA-1*023:01. With IFN-γ ELISPOT and peptide–MHC class I Tet staining assays on two parasite-specific bovine CTL lines, we showed that amino acids at positions 5–8 in the epitope were required for TCR recognition. Only two of eight naturally occurring polymorphic Tp9 epitopes were recognized by both CTLs. Finally, using a TCR avidity assay, we found that a higher TCR avidity was associated with a stronger functional response toward one of two variants recognized by the CTL. These data add to the growing knowledge on the cross-reactivity of epitope-specific CTLs and specificities that may be required in the selection of Ags in the design of a wide-spectrum vaccine for East Coast fever. |
Databáze: | OpenAIRE |
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