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Determination of IgG1 and IgG3 SARS-CoV-2 Spike Protein and Nucleocapsid Binding-Who Is Binding Who and Why?

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cam.issuedOnline2022-05-27
dc.contributor.authorIles, Jason K
dc.contributor.authorZmuidinaite, Raminta
dc.contributor.authorSadee, Christoph
dc.contributor.authorGardiner, Anna
dc.contributor.authorLacey, Jonathan
dc.contributor.authorHarding, Stephen
dc.contributor.authorWallis, Gregg
dc.contributor.authorPatel, Roshani
dc.contributor.authorRoblett, Debra
dc.contributor.authorHeeney, Jonathan
dc.contributor.authorBaxendale, Helen
dc.contributor.authorIles, Ray Kruse
dc.contributor.orcidZmuidinaite, Raminta [0000-0001-7728-6623]
dc.date.accessioned2022-05-30T15:02:39Z
dc.date.available2022-05-30T15:02:39Z
dc.date.issued2022-05-27
dc.date.updated2022-05-30T15:02:39Z
dc.description.abstractThe involvement of immunoglobulin (Ig) G3 in the humoral immune response to SARS-CoV-2 infection has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) in COVID-19. The exact molecular mechanism is unknown, but it is thought to involve this IgG subtype's differential ability to fix, complement and stimulate cytokine release. We examined the binding of convalescent patient antibodies to immobilized nucleocapsids and spike proteins by matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry. IgG3 was a major immunoglobulin found in all samples. Differential analysis of the spectral signatures found for the nucleocapsid versus the spike protein demonstrated that the predominant humoral immune response to the nucleocapsid was IgG3, whilst for the spike protein it was IgG1. However, the spike protein displayed a strong affinity for IgG3 itself, as it would bind from control plasma samples, as well as from those previously infected with SARS-CoV-2, similar to the way protein G binds IgG1. Furthermore, detailed spectral analysis indicated that a mass shift consistent with hyper-glycosylation or glycation was a characteristic of the IgG3 captured by the spike protein.
dc.identifier.doi10.17863/CAM.85014
dc.identifier.eissn1422-0067
dc.identifier.issn1422-0067
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337605
dc.languageen
dc.publisherMDPI AG
dc.subjectCOVID-19
dc.subjectconvalescent plasma
dc.subjectspike protein
dc.subjectnucleocapsid
dc.subjectIgG1
dc.subjectIgG3
dc.subjectpredictive profile
dc.titleDetermination of IgG1 and IgG3 SARS-CoV-2 Spike Protein and Nucleocapsid Binding-Who Is Binding Who and Why?
dc.typeArticle
dcterms.dateAccepted2022-05-25
prism.issueIdentifier11
prism.publicationNameInt J Mol Sci
prism.volume23
pubs.funder-project-idNational Institute for Health Research (G107217)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.3390/ijms23116050

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