An immunodominant NP<inf>105–113</inf>-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease

Peng Y.Felce S.L.Dong D.Penkava F.Mentzer A.J.Yao X.Liu G.Yin Z.Chen J.L.Lu Y.Wellington D.Wing P.A.C.Dominey-Foy D.C.C.Jin C.Wang W.Hamid M.A.Fernandes R.A.Wang B.Fries A.Zhuang X.Ashley N.Rostron T.Waugh C.Sopp P.Hublitz P.Beveridge R.Tan T.K.Dold C.Kwok A.J.Rich-Griffin C.Dejnirattisa W.Liu C.Kurupati P.Nassiri I.Watson R.A.Tong O.Taylor C.A.Kumar Sharma P.Sun B.Curion F.Revale S.Garner L.C.Jansen K.Ferreira R.C.Attar M.Fry J.W.Russell R.A.Stauss H.J.James W.Townsend A.Ho L.P.Klenerman P.Mongkolsapaya J.Screaton G.R.Dendrou C.Sansom S.N.Bashford-Rogers R.Chain B.Smith G.L.McKeating J.A.Fairfax B.P.Bowness P.McMichael A.J.Ogg G.Knight J.C.Dong T.Mahidol University2023-06-182023-06-182022-01-01Nature Immunology Vol.23 No.1 (2022) , 50-6115292908https://repository.li.mahidol.ac.th/handle/20.500.14594/85063NP105–113-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.Immunology and MicrobiologyAn immunodominant NP<inf>105–113</inf>-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 diseaseArticleSCOPUS10.1038/s41590-021-01084-z2-s2.0-851206345091529291634853448