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
cg.contributor.affiliationInternational Livestock Research Instituteen
cg.contributor.affiliationChinese Academy of Agricultural Sciencesen
cg.contributor.crpLivestock
cg.contributor.donorBill & Melinda Gates Foundationen
cg.contributor.donorGovernment of the United Kingdomen
cg.contributor.donorUnited States Agency for International Developmenten
cg.contributor.donorUnited States Department of Agricultureen
cg.creator.identifierNicholas Svitek: 0000-0002-4539-5806
cg.creator.identifierVishvanath Nene: 0000-0001-7066-4169
cg.creator.identifierLucilla Steinaa: 0000-0003-3691-3971
cg.howPublishedFormally Publisheden
cg.identifier.doihttps://doi.org/10.4049/jimmunol.2100400en
cg.isijournalISI Journalen
cg.issn0022-1767en
cg.issue3en
cg.journalJournal of Immunologyen
cg.reviewStatusPeer Reviewen
cg.subject.ilriECFen
cg.subject.ilriVACCINESen
cg.subject.impactAreaNutrition, health and food security
cg.subject.sdgSDG 2 - Zero hungeren
cg.volume208en
dc.contributor.authorSvitek, Nicholasen
dc.contributor.authorSaya, Rosemaryen
dc.contributor.authorHoushuang Zhangen
dc.contributor.authorNene, Vishvanath M.en
dc.contributor.authorSteinaa, Lucillaen
dc.date.accessioned2022-01-17T14:52:15Zen
dc.date.available2022-01-17T14:52:15Zen
dc.identifier.urihttps://hdl.handle.net/10568/117535
dc.titleSystematic determination of TCR-antigen and peptide-MHC binding kinetics among field variants of a Theileria parva polymorphic CTL epitopeen
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
dcterms.accessRightsOpen Access
dcterms.audienceAcademicsen
dcterms.audienceScientistsen
dcterms.available2022-02-01
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
dcterms.extent549-561en
dcterms.issued2022-02-01
dcterms.languageen
dcterms.licenseCC-BY-4.0
dcterms.publisherAmerican Association of Immunologistsen
dcterms.subjectimmunologyen
dcterms.subjectvaccinesen
dcterms.subjecteast coast feveren
dcterms.typeJournal Article

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ILRI animal and human health program outputs (2017–2024)
Improved vaccines for the control of East Coast fever in cattle in Africa