Fully phased population-prevalent East African cattle BoLA-I alleles determined using PacBio HiFi long-read sequencing represent five novel specificities with distinctive peptide binding potential

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cg.authorship.typesCGIAR and developing country instituteen
cg.authorship.typesCGIAR and advanced research instituteen
cg.contributor.affiliationFreie Universität Berlinen
cg.contributor.affiliationUniversity of Edinburghen
cg.contributor.affiliationTechnical University of Denmarken
cg.contributor.affiliationInternational Livestock Research Instituteen
cg.contributor.affiliationMakerere Universityen
cg.contributor.affiliationWashington State Universityen
cg.contributor.donorDeutsche Forschungsgemeinschaften
cg.contributor.donorProjekt DEALen
cg.coverage.countryKenyaen
cg.coverage.countryTanzaniaen
cg.coverage.countryUgandaen
cg.coverage.iso3166-alpha2KEen
cg.coverage.iso3166-alpha2TZen
cg.coverage.iso3166-alpha2UGen
cg.coverage.regionAfricaen
cg.coverage.regionEastern Africaen
cg.coverage.regionSouthern Africaen
cg.creator.identifierNaftaly Githaka: 0000-0003-4530-7164en
cg.creator.identifierRichard Bishop: 0000-0002-3720-9970en
cg.howPublishedFormally Publisheden
cg.identifier.doihttps://doi.org/10.1111/tan.70183en
cg.isijournalISI Journalen
cg.issn2059-2302en
cg.issue4en
cg.journalHLA: Immune Response Geneticsen
cg.reviewStatusPeer Reviewen
cg.subject.ilriCATTLEen
cg.subject.sdgSDG 2 - Zero hungeren
cg.volume105en
dc.contributor.authorObara, I.en
dc.contributor.authorSandro, A.en
dc.contributor.authorElati, K.en
dc.contributor.authorConneley, T.en
dc.contributor.authorNielsen, M.en
dc.contributor.authorGithaka, Naftaly W.en
dc.contributor.authorNanteza, A.en
dc.contributor.authorBishop, Richard P.en
dc.contributor.authorNijhof, A.en
dc.date.accessioned2025-04-22T06:11:31Zen
dc.date.available2025-04-22T06:11:31Zen
dc.identifier.urihttps://hdl.handle.net/10568/174272
dc.titleFully phased population-prevalent East African cattle BoLA-I alleles determined using PacBio HiFi long-read sequencing represent five novel specificities with distinctive peptide binding potentialen
dcterms.abstractDue to factors such as lower biosecurity, greater wildlife/farm animal interfaces, and environmental challenges, cattle in sub-Saharan Africa are exposed to more diverse and intensive bacterial, viral and protozoan pathogen challenges than cattle in Europe and other high-income regions of the world. Classical class I genes of the major histocompatibility complex (MHC) contribute to protection from diseases caused by these pathogens by refining a huge pool of potential pathogen-derived peptide ligands into a smaller ensemble for presentation to CD8+ T cells. Knowledge of population-prevalent MHC alleles is therefore critical for evidence-based approaches to vaccine design and improved understanding of pathogen resistance. Whereas variation in MHC molecules is understood in most detail for European <i>Bos taurus</i>, the alleles expressed by Africa's cattle remain poorly defined. We have leveraged recent improvements in the accuracy of PacBio high-fidelity (HiFi) circular consensus sequencing (CCS) and adapted stringent sequence filtering algorithms to identify hundreds of as yet uncharacterised fully phased BoLA-I alleles from multiple populations of African taurine (Ankole) and indicine (Zebu) cattle in East Africa. The analysis highlights a convergence of population-prevalent class I MHC allelic repertoires in taurine and indicine cattle, likely due to the similar pathogen-driven selective pressures. Our analysis of the anchor residue accommodating pockets of these prevalent alleles revealed extremely high levels of polymorphism, which contrast with Holstein alleles that exhibit a more limited repertoire of MHC specificity-determining pocket residues, potentially constraining the breadth of peptide presentation. However, in the context of considerable sequence and physicochemical variation in the pocket-forming residues, it was possible to discern overlaps in the predicted peptide binding spectrum. Interrogation of potential differences in peptide binding specificities with European <i>B. taurus</i> alleles revealed that the fully phased African cattle class I MHC alleles represent five novel specificities. We envisage that this novel finding will find broad application in assessing potentially achievable vaccination coverages of future pathogen-encoded vaccine candidates against important intracellular pathogens. One aim of future research should be to leverage recent improvements in the sensitivity of mass spectrometry combined with immunoprecipitation of peptides bound to African cattle MHC to search directly for T-cell epitopes in the context of the inferred ‘supertype’ diversity.en
dcterms.accessRightsOpen Accessen
dcterms.audienceAcademicsen
dcterms.audienceScientistsen
dcterms.available2025-04-17en
dcterms.bibliographicCitationObara, I., Sandro, A., Elati, K., Conneley, T., Nielsen, M., Githaka, N., Nanteza, A., Bishop, R. and Nijhof, A. 2025. Fully phased population-prevalent East African cattle BoLA-I alleles determined using PacBio HiFi long-read sequencing represent five novel specificities with distinctive peptide binding potential. HLA: Immune Response Genetics 105(4): e70183.en
dcterms.extente70183en
dcterms.issued2025-04-17en
dcterms.languageenen
dcterms.licenseCC-BY-4.0en
dcterms.publisherWileyen
dcterms.subjectcattleen
dcterms.typeJournal Articleen

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