Systematic determination of TCR-antigen and peptide-MHC binding kinetics among field variants of a Theileria parva polymorphic CTL epitope
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...
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Language: | Inglés |
| Published: |
Oxford University Press
2022
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10568/117535 |
| _version_ | 1855526340876304384 |
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| author | Svitek, Nicholas Saya, Rosemary Houshuang Zhang Nene, Vishvanath M. Steinaa, Lucilla |
| author_browse | Houshuang Zhang Nene, Vishvanath M. Saya, Rosemary Steinaa, Lucilla Svitek, Nicholas |
| author_facet | Svitek, Nicholas Saya, Rosemary Houshuang Zhang Nene, Vishvanath M. Steinaa, Lucilla |
| author_sort | Svitek, Nicholas |
| collection | Repository of Agricultural Research Outputs (CGSpace) |
| description | 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. |
| format | Journal Article |
| id | CGSpace117535 |
| institution | CGIAR Consortium |
| language | Inglés |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Oxford University Press |
| publisherStr | Oxford University Press |
| record_format | dspace |
| spelling | CGSpace1175352025-10-26T13:00:35Z Systematic determination of TCR-antigen and peptide-MHC binding kinetics among field variants of a Theileria parva polymorphic CTL epitope Svitek, Nicholas Saya, Rosemary Houshuang Zhang Nene, Vishvanath M. Steinaa, Lucilla immunology vaccines east coast fever 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. 2022-02-01 2022-01-17T14:52:15Z 2022-01-17T14:52:15Z Journal Article https://hdl.handle.net/10568/117535 en Open Access Oxford University Press Svitek, N., Saya, R., Zhang, H., Nene, V. and Steinaa, L. 2022. Systematic determination of TCR-antigen and peptide-MHC binding kinetics among field variants of a Theileria parva polymorphic CTL epitope. Journal of Immunology 208(3): 549–561. |
| spellingShingle | immunology vaccines east coast fever Svitek, Nicholas Saya, Rosemary Houshuang Zhang Nene, Vishvanath M. Steinaa, Lucilla Systematic determination of TCR-antigen and peptide-MHC binding kinetics among field variants of a Theileria parva polymorphic CTL epitope |
| title | Systematic determination of TCR-antigen and peptide-MHC binding kinetics among field variants of a Theileria parva polymorphic CTL epitope |
| title_full | Systematic determination of TCR-antigen and peptide-MHC binding kinetics among field variants of a Theileria parva polymorphic CTL epitope |
| title_fullStr | Systematic determination of TCR-antigen and peptide-MHC binding kinetics among field variants of a Theileria parva polymorphic CTL epitope |
| title_full_unstemmed | Systematic determination of TCR-antigen and peptide-MHC binding kinetics among field variants of a Theileria parva polymorphic CTL epitope |
| title_short | Systematic determination of TCR-antigen and peptide-MHC binding kinetics among field variants of a Theileria parva polymorphic CTL epitope |
| title_sort | systematic determination of tcr antigen and peptide mhc binding kinetics among field variants of a theileria parva polymorphic ctl epitope |
| topic | immunology vaccines east coast fever |
| url | https://hdl.handle.net/10568/117535 |
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