The SARS-CoV-2 Omicron BA.1 spike G446S mutation potentiates antiviral T-cell recognition.
The SARS-CoV-2 Omicron BA.1 spike G446S mutation potentiates antiviral T-cell recognition.
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DOI：
10.1038/s41467-022-33068-4
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发表时间：
2022-09-21
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
虽然SARS-CoV-2病毒的Omicron变体显示出对中和抗体的抗性，但它保留了对细胞免疫应答的敏感性。在这里，我们描述了疫苗诱导的T细胞对各种SARS-CoV-2变异体的特异性，并鉴定了HLA-A*24：02限制性CD 8 + T细胞，其在体外强烈抑制Omicron BA.1复制。突变分析显示，G446 S突变，位于同源表位的N-末端外，增强了TCR对该变体的识别。相比之下，没有观察到针对用表达G446的原型、Omicron BA.2和Delta变体感染的细胞的增强的复制抑制。当靶细胞用三肽基肽酶II（一种介导抗原加工的蛋白质）的抑制剂处理时，G446 S突变的增强作用丧失。这些离体分析和体外结果表明，Omicron BA.1变体中的G446 S突变影响抗原加工/呈递，并通过疫苗诱导的T细胞增强抗病毒活性，导致T细胞对新出现的变体的识别增强。SARS-CoV-2刺突中的突变可导致中和抗体反应的逃逸，但可能保留对细胞免疫反应的易感性。在这里，作者表明，Omicron BA.1刺突蛋白中的G446 S突变与抗原呈递的改变有关，并增强了特异性T细胞免疫的激活。
Although the Omicron variant of the SARS-CoV-2 virus shows resistance to neutralizing antibody, it retains susceptibility to the cellular immune response. Here we characterize vaccine-induced T cells specific for various SARS-CoV-2 variants and identified HLA-A*24:02-restricted CD8+ T cells that strongly suppress Omicron BA.1 replication in vitro. Mutagenesis analyses revealed that a G446S mutation, located just outside the N-terminus of the cognate epitope, augmented TCR recognition of this variant. In contrast, no enhanced suppression of replication is observed against cells infected with the prototype, Omicron BA.2, and Delta variants that express G446. The enhancing effect of the G446S mutation is lost when target cells are treated with inhibitors of tripeptidyl peptidase II, a protein that mediates antigen processing. These ex vivo analysis and in vitro results demonstrate that the G446S mutation in the Omicron BA.1 variant affects antigen processing/presentation and potentiates antiviral activity by vaccine-induced T cells, leading to enhanced T cell recognition towards emerging variants. Mutations in the spike of SARS-CoV-2 can result in the escape of the neutralising antibody response but may retain susceptibility to the cellular immune response. Here the authors show the G446S mutation in the spike protein of Omicron BA.1 is associated with altered antigen presentation and potentiates activation of specific T cell immunity.
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影响因子：
82.9
作者：
Gao Y;Cai C;Grifoni A;Müller TR;Niessl J;Olofsson A;Humbert M;Hansson L;Österborg A;Bergman P;Chen P;Olsson A;Sandberg JK;Weiskopf D;Price DA;Ljunggren HG;Karlsson AC;Sette A;Aleman S;Buggert M
通讯作者：
Buggert M
影响因子：
5.8
作者：
Gao A;Chen Z;Amitai A;Doelger J;Mallajosyula V;Sundquist E;Pereyra Segal F;Carrington M;Davis MM;Streeck H;Chakraborty AK;Julg B
通讯作者：
Julg B
影响因子：
8.8
作者：
Kimura I;Kosugi Y;Wu J;Zahradnik J;Yamasoba D;Butlertanaka EP;Tanaka YL;Uriu K;Liu Y;Morizako N;Shirakawa K;Kazuma Y;Nomura R;Horisawa Y;Tokunaga K;Ueno T;Takaori-Kondo A;Schreiber G;Arase H;Genotype to Phenotype Japan (G2P-Japan) Consortium;Motozono C;Saito A;Nakagawa S;Sato K
通讯作者：
Sato K
影响因子：
24.8
作者：
GeurtsvanKessel CH;Geers D;Schmitz KS;Mykytyn AZ;Lamers MM;Bogers S;Scherbeijn S;Gommers L;Sablerolles RSG;Nieuwkoop NN;Rijsbergen LC;van Dijk LLA;de Wilde J;Alblas K;Breugem TI;Rijnders BJA;de Jager H;Weiskopf D;van der Kuy PHM;Sette A;Koopmans MPG;Grifoni A;Haagmans BL;de Vries RD
通讯作者：
de Vries RD
影响因子：
30.5
作者：
Peng, Yanchun;Mentzer, Alexander J.;Dong, Tao
通讯作者：
Dong, Tao