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An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

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cam.issuedOnline2021-12
dc.contributor.authorPeng, Yanchun
dc.contributor.authorFelce, Suet Ling
dc.contributor.authorDong, Danning
dc.contributor.authorPenkava, Frank
dc.contributor.authorMentzer, Alexander J
dc.contributor.authorYao, Xuan
dc.contributor.authorLiu, Guihai
dc.contributor.authorYin, Zixi
dc.contributor.authorChen, Ji-Li
dc.contributor.authorLu, Yongxu
dc.contributor.authorWellington, Dannielle
dc.contributor.authorWing, Peter AC
dc.contributor.authorDominey-Foy, Delaney CC
dc.contributor.authorJin, Chen
dc.contributor.authorWang, Wenbo
dc.contributor.authorHamid, Megat Abd
dc.contributor.authorFernandes, Ricardo A
dc.contributor.authorWang, Beibei
dc.contributor.authorFries, Anastasia
dc.contributor.authorZhuang, Xiaodong
dc.contributor.authorAshley, Neil
dc.contributor.authorRostron, Timothy
dc.contributor.authorWaugh, Craig
dc.contributor.authorSopp, Paul
dc.contributor.authorHublitz, Philip
dc.contributor.authorBeveridge, Ryan
dc.contributor.authorTan, Tiong Kit
dc.contributor.authorDold, Christina
dc.contributor.authorKwok, Andrew J
dc.contributor.authorRich-Griffin, Charlotte
dc.contributor.authorDejnirattisa, Wanwisa
dc.contributor.authorLiu, Chang
dc.contributor.authorKurupati, Prathiba
dc.contributor.authorNassiri, Isar
dc.contributor.authorWatson, Robert A
dc.contributor.authorTong, Orion
dc.contributor.authorTaylor, Chelsea A
dc.contributor.authorKumar Sharma, Piyush
dc.contributor.authorSun, Bo
dc.contributor.authorCurion, Fabiola
dc.contributor.authorRevale, Santiago
dc.contributor.authorGarner, Lucy C
dc.contributor.authorJansen, Kathrin
dc.contributor.authorFerreira, Ricardo C
dc.contributor.authorAttar, Moustafa
dc.contributor.authorFry, Jeremy W
dc.contributor.authorRussell, Rebecca A
dc.contributor.authorCOMBAT Consortium
dc.contributor.authorStauss, Hans J
dc.contributor.authorJames, William
dc.contributor.authorTownsend, Alain
dc.contributor.authorHo, Ling-Pei
dc.contributor.authorKlenerman, Paul
dc.contributor.authorMongkolsapaya, Juthathip
dc.contributor.authorScreaton, Gavin R
dc.contributor.authorDendrou, Calliope
dc.contributor.authorSansom, Stephen N
dc.contributor.authorBashford-Rogers, Rachael
dc.contributor.authorChain, Benny
dc.contributor.authorSmith, Geoffrey L
dc.contributor.authorMcKeating, Jane A
dc.contributor.authorFairfax, Benjamin P
dc.contributor.authorBowness, Paul
dc.contributor.authorMcMichael, Andrew J
dc.contributor.authorOgg, Graham
dc.contributor.authorKnight, Julian C
dc.contributor.authorDong, Tao
dc.contributor.orcidPeng, Yanchun [0000-0003-2340-0499]
dc.contributor.orcidPenkava, Frank [0000-0001-9163-8576]
dc.contributor.orcidMentzer, Alexander J [0000-0002-4502-2209]
dc.contributor.orcidYin, Zixi [0000-0002-2044-5838]
dc.contributor.orcidWing, Peter AC [0000-0002-2354-3281]
dc.contributor.orcidFries, Anastasia [0000-0003-1609-5991]
dc.contributor.orcidZhuang, Xiaodong [0000-0002-6870-9003]
dc.contributor.orcidHublitz, Philip [0000-0001-8810-3247]
dc.contributor.orcidTan, Tiong Kit [0000-0001-8746-8308]
dc.contributor.orcidKwok, Andrew J [0000-0001-8928-5054]
dc.contributor.orcidRich-Griffin, Charlotte [0000-0001-8212-9542]
dc.contributor.orcidTong, Orion [0000-0002-0659-5944]
dc.contributor.orcidKumar Sharma, Piyush [0000-0002-6247-3503]
dc.contributor.orcidSun, Bo [0000-0002-5507-6657]
dc.contributor.orcidGarner, Lucy C [0000-0002-6461-252X]
dc.contributor.orcidJansen, Kathrin [0000-0002-3803-7680]
dc.contributor.orcidAttar, Moustafa [0000-0003-4116-1276]
dc.contributor.orcidFry, Jeremy W [0000-0003-3689-6606]
dc.contributor.orcidRussell, Rebecca A [0000-0002-6517-6483]
dc.contributor.orcidStauss, Hans J [0000-0003-4340-7911]
dc.contributor.orcidJames, William [0000-0002-2506-1198]
dc.contributor.orcidKlenerman, Paul [0000-0003-4307-9161]
dc.contributor.orcidMongkolsapaya, Juthathip [0000-0003-3416-9480]
dc.contributor.orcidScreaton, Gavin R [0000-0002-3549-4309]
dc.contributor.orcidSansom, Stephen N [0000-0003-4569-8513]
dc.contributor.orcidBashford-Rogers, Rachael [0000-0002-6838-0711]
dc.contributor.orcidChain, Benny [0000-0002-7417-3970]
dc.contributor.orcidSmith, Geoffrey L [0000-0002-3730-9955]
dc.contributor.orcidBowness, Paul [0000-0003-4597-0484]
dc.contributor.orcidDong, Tao [0000-0003-3545-3758]
dc.date.accessioned2022-01-06T11:50:04Z
dc.date.available2022-01-06T11:50:04Z
dc.date.issued2022-01
dc.date.submitted2021-07-19
dc.date.updated2022-01-06T11:50:03Z
dc.descriptionFunder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265
dc.descriptionFunder: Chinese Academy of Medical Sciences (CAMS); doi: https://doi.org/10.13039/501100005150
dc.descriptionFunder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440
dc.description.abstractNP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.
dc.identifier.doi10.17863/CAM.79594
dc.identifier.eissn1529-2916
dc.identifier.issn1529-2908
dc.identifier.others41590-021-01084-z
dc.identifier.other1084
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332148
dc.languageen
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41590-021-01084-z
dc.subjectAged
dc.subjectAmino Acid Sequence
dc.subjectAntibodies, Viral
dc.subjectAntibody Affinity
dc.subjectCOVID-19
dc.subjectCell Line, Transformed
dc.subjectFemale
dc.subjectGene Expression Profiling
dc.subjectHLA-B7 Antigen
dc.subjectHumans
dc.subjectImmunodominant Epitopes
dc.subjectImmunologic Memory
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectNucleocapsid Proteins
dc.subjectReceptors, Antigen, T-Cell
dc.subjectSARS-CoV-2
dc.subjectSeverity of Illness Index
dc.subjectT-Lymphocytes, Cytotoxic
dc.subjectVaccinia virus
dc.titleAn immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.
dc.typeArticle
dcterms.dateAccepted2021-10-26
prism.endingPage61
prism.issueIdentifier1
prism.publicationNameNat Immunol
prism.startingPage50
prism.volume23
pubs.funder-project-idWellcome Trust (090315/Z/09/Z)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41590-021-01084-z

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