An immunodominant NP(105-113)-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.
An immunodominant NP(105-113)-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.
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DOI：
10.1038/s41590-021-01084-z
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发表时间：
2022-01
影响因子：
30.5
通讯作者：
Dong T
中科院分区：
文献类型：
--
作者：
Peng Y;Felce SL;Dong D;Penkava F;Mentzer AJ;Yao X;Liu G;Yin Z;Chen JL;Lu Y;Wellington D;Wing PAC;Dominey-Foy DCC;Jin C;Wang W;Hamid MA;Fernandes RA;Wang B;Fries A;Zhuang X;Ashley N;Rostron T;Waugh C;Sopp P;Hublitz P;Beveridge R;Tan TK;Dold C;Kwok AJ;Rich-Griffin C;Dejnirattisa W;Liu C;Kurupati P;Nassiri I;Watson RA;Tong O;Taylor CA;Kumar Sharma P;Sun B;Curion F;Revale S;Garner LC;Jansen K;Ferreira RC;Attar M;Fry JW;Russell RA;COMBAT Consortium;Stauss HJ;James W;Townsend A;Ho LP;Klenerman P;Mongkolsapaya J;Screaton GR;Dendrou C;Sansom SN;Bashford-Rogers R;Chain B;Smith GL;McKeating JA;Fairfax BP;Bowness P;McMichael AJ;Ogg G;Knight JC;Dong T
NP105-113-B *07:02特异性CD8+ T细胞应答被认为是sars - cov -2感染个体中最主要的应答。我们发现这种反应与轻度疾病有很强的联系。同时进行NP105-113-B *07:02特异性T细胞克隆分析和单细胞测序，利用体外SARS-CoV-2感染系统评估功能亲和度和抗病毒疗效，并与T细胞受体使用、转录组特征和疾病严重程度（急性期77例，恢复期52例）相关。我们证实了NP105-113-B *07:02特异性T细胞在COVID-19疾病进展中的有益关联，与T细胞前体的扩增、高功能亲和性和抗病毒效应功能有关。感染后广泛的免疫记忆池缩小，但NP105-113-B *07:02-特异性T细胞在感染后6个月仍保持对SARS-CoV-2维多利亚株以及α、β、γ和δ变体的抗病毒作用。我们的数据显示，NP105-113-B *07:02特异性T细胞反应与轻度疾病和高抗病毒效果相关，为未来的疫苗设计指明了方向。Peng等人发现特异性NP105-113-B *07:02的免疫显性细胞毒性T淋巴细胞（ctl）与降低COVID-19严重程度相关。从机制上讲，NP105-113-B *07:02特异性ctl显示出有效的抗病毒功能，可能是合理的T细胞疫苗靶点。
NP105–113-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. Peng et al. find that immunodominant cytotoxic T lymphocytes (CTLs) specific for NP105–113-B*07:02 are associated with reduced COVID-19 severity. Mechanistically, NP105–113-B*07:02-specific CTLs show potent antiviral functionality and may represent rational T cell vaccine targets.
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影响因子：
46.9
作者：
Bolotin DA;Poslavsky S;Davydov AN;Frenkel FE;Fanchi L;Zolotareva OI;Hemmers S;Putintseva EV;Obraztsova AS;Shugay M;Ataullakhanov RI;Rudensky AY;Schumacher TN;Chudakov DM
通讯作者：
Chudakov DM
影响因子：
10.1
作者：
Abd Hamid M;Colin-York H;Khalid-Alham N;Browne M;Cerundolo L;Chen JL;Yao X;Rosendo-Machado S;Waugh C;Maldonado-Perez D;Bowes E;Verrill C;Cerundolo V;Conlon CP;Fritzsche M;Peng Y;Dong T
通讯作者：
Dong T
影响因子：
32.4
作者：
Ferretti AP;Kula T;Wang Y;Nguyen DMV;Weinheimer A;Dunlap GS;Xu Q;Nabilsi N;Perullo CR;Cristofaro AW;Whitton HJ;Virbasius A;Olivier KJ Jr;Buckner LR;Alistar AT;Whitman ED;Bertino SA;Chattopadhyay S;MacBeath G
通讯作者：
MacBeath G
影响因子：
7.3
作者：
Peng Y;Wang B;Talaat K;Karron R;Powell TJ;Zeng H;Dong D;Luke CJ;McMichael A;Subbarao K;Dong T
通讯作者：
Dong T
影响因子：
16.6
作者：
Akthar S;Patel DF;Beale RC;Peiró T;Xu X;Gaggar A;Jackson PL;Blalock JE;Lloyd CM;Snelgrove RJ
通讯作者：
Snelgrove RJ