Systematic determination of TCR-antigen and peptide-MHC binding kinetics among field variants of a Theileria parva polymorphic CTL epitope

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cg.authorship.typesCGIAR and developing country instituteen_US
cg.contributor.affiliationInternational Livestock Research Instituteen_US
cg.contributor.affiliationChinese Academy of Agricultural Sciencesen_US
cg.contributor.crpLivestocken_US
cg.contributor.donorBill & Melinda Gates Foundationen_US
cg.contributor.donorGovernment of the United Kingdomen_US
cg.contributor.donorUnited States Agency for International Developmenten_US
cg.contributor.donorUnited States Department of Agricultureen_US
cg.creator.identifierNicholas Svitek: 0000-0002-4539-5806en_US
cg.creator.identifierVishvanath Nene: 0000-0001-7066-4169en_US
cg.creator.identifierLucilla Steinaa: 0000-0003-3691-3971en_US
cg.howPublishedFormally Publisheden_US
cg.identifier.doihttps://doi.org/10.4049/jimmunol.2100400en_US
cg.isijournalISI Journalen_US
cg.issn0022-1767en_US
cg.issue3en_US
cg.journalJournal of Immunologyen_US
cg.reviewStatusPeer Reviewen_US
cg.subject.ilriECFen_US
cg.subject.ilriVACCINESen_US
cg.subject.impactAreaNutrition, health and food securityen_US
cg.subject.sdgSDG 2 - Zero hungeren_US
cg.volume208en_US
dc.contributor.authorSvitek, Nicholasen_US
dc.contributor.authorSaya, Rosemaryen_US
dc.contributor.authorHoushuang Zhangen_US
dc.contributor.authorNene, Vishvanath M.en_US
dc.contributor.authorSteinaa, Lucillaen_US
dc.date.accessioned2022-01-17T14:52:15Zen_US
dc.date.available2022-01-17T14:52:15Zen_US
dc.identifier.urihttps://hdl.handle.net/10568/117535en_US
dc.titleSystematic determination of TCR-antigen and peptide-MHC binding kinetics among field variants of a Theileria parva polymorphic CTL epitopeen_US
dcterms.abstractCTLs 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.en_US
dcterms.accessRightsOpen Accessen_US
dcterms.audienceAcademicsen_US
dcterms.audienceScientistsen_US
dcterms.available2022-02-01en_US
dcterms.bibliographicCitationSvitek, 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.en_US
dcterms.extent549-561en_US
dcterms.issued2022-02-01en_US
dcterms.languageenen_US
dcterms.licenseCC-BY-4.0en_US
dcterms.publisherAmerican Association of Immunologistsen_US
dcterms.subjectimmunologyen_US
dcterms.subjectvaccinesen_US
dcterms.subjecteast coast feveren_US
dcterms.typeJournal Articleen_US

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Improved vaccines for the control of East Coast fever in cattle in Africa