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dc.contributor.authorKockelbergh, Hannah
dc.contributor.authorEvans, Shelley
dc.contributor.authorDeng, Tong
dc.contributor.authorClyne, Ella
dc.contributor.authorKyriakidou, Anna
dc.contributor.authorEconomou, Andreas
dc.contributor.authorLuu Hoang, Kim Ngan
dc.contributor.authorWoodmansey, Stephen
dc.contributor.authorFoers, Andrew
dc.contributor.authorFowler, Anna
dc.contributor.authorSoilleux, Elizabeth J
dc.date.accessioned2022-06-29T19:48:26Z
dc.date.available2022-06-29T19:48:26Z
dc.date.issued2022-05-13
dc.identifier.citationDiagnostics (Basel, Switzerland), volume 12, issue 5, page 1222
dc.identifier.issn2075-4418
dc.identifier.other35626377
dc.identifier.otherPMC9140453
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338564
dc.description.abstractMeasuring immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19), can rely on antibodies, reactive T cells and other factors, with T-cell-mediated responses appearing to have greater sensitivity and longevity. Because each T cell carries an essentially unique nucleic acid sequence for its T-cell receptor (TCR), we can interrogate sequence data derived from DNA or RNA to assess aspects of the immune response. This review deals with the utility of bulk, rather than single-cell, sequencing of TCR repertoires, considering the importance of study design, in terms of cohort selection, laboratory methods and analysis. The advances in understanding SARS-CoV-2 immunity that have resulted from bulk TCR repertoire sequencing are also be discussed. The complexity of sequencing data obtained by bulk repertoire sequencing makes analysis challenging, but simple descriptive analyses, clonal analysis, searches for specific sequences associated with immune responses to SARS-CoV-2, motif-based analyses, and machine learning approaches have all been applied. TCR repertoire sequencing has demonstrated early expansion followed by contraction of SARS-CoV-2-specific clonotypes, during active infection. Maintenance of TCR repertoire diversity, including the maintenance of diversity of anti-SARS-CoV-2 response, predicts a favourable outcome. TCR repertoire narrowing in severe COVID-19 is most likely a consequence of COVID-19-associated lymphopenia. It has been possible to follow clonotypic sequences longitudinally, which has been particularly valuable for clonotypes known to be associated with SARS-CoV-2 peptide/MHC tetramer binding or with SARS-CoV-2 peptide-induced cytokine responses. Closely related clonotypes to these previously identified sequences have been shown to respond with similar kinetics during infection. A possible superantigen-like effect of the SARS-CoV-2 spike protein has been identified, by means of observing V-segment skewing in patients with severe COVID-19, together with structural modelling. Such a superantigen-like activity, which is apparently absent from other coronaviruses, may be the basis of multisystem inflammatory syndrome and cytokine storms in COVID-19. Bulk TCR repertoire sequencing has proven to be a useful and cost-effective approach to understanding interactions between SARS-CoV-2 and the human host, with the potential to inform the design of therapeutics and vaccines, as well as to provide invaluable pathogenetic and epidemiological insights.
dc.languageeng
dc.publisherMDPI AG
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2075-4418
dc.sourcenlmid: 101658402
dc.subjectDiversity
dc.subjectAntibody
dc.subjectImmune response
dc.subjectCoronavirus
dc.subjectMachine Learning
dc.subjectImmunological Memory
dc.subjectT-cell Receptor Repertoire
dc.subjectImmunoreceptor
dc.subjectCovid-19
dc.subjectSars-cov-2
dc.titleUtility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19.
dc.typeArticle
dc.date.updated2022-06-29T19:48:26Z
prism.publicationNameDiagnostics (Basel)
dc.identifier.doi10.17863/CAM.85977
dcterms.dateAccepted2022-05-10
rioxxterms.versionofrecord10.3390/diagnostics12051222
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidEvans, Shelley [0000-0003-3242-6017]
dc.contributor.orcidClyne, Ella [0000-0001-8945-4508]
dc.contributor.orcidKyriakidou, Anna [0000-0001-8964-8345]
dc.contributor.orcidEconomou, Andreas [0000-0002-3305-5804]
dc.contributor.orcidLuu Hoang, Kim Ngan [0000-0001-5670-1832]
dc.contributor.orcidFoers, Andrew [0000-0002-5036-7906]
dc.contributor.orcidSoilleux, Elizabeth J [0000-0002-4032-7249]
dc.identifier.eissn2075-4418
cam.issuedOnline2022-05-13


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International