Structural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors.
Structural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors.
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DOI：
10.1038/s41467-021-27669-8
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发表时间：
2022-01-10
影响因子：
16.6
通讯作者：
Mariuzza RA
中科院分区：
文献类型：
--
作者：
Wu D;Kolesnikov A;Yin R;Guest JD;Gowthaman R;Shmelev A;Serdyuk Y;Dianov DV;Efimov GA;Pierce BG;Mariuzza RA
T细胞在对抗SARS-CoV-2和形成长期记忆反应方面起着至关重要的作用。尽管关于SARS-CoV-2的中和抗体的广泛结构信息是可用的，但是关于结合到其肽-MHC靶点的SARS-CoV-2特异性T细胞受体（TCR）的此类信息是缺乏的。在这里，我们确定了来自COVID-19恢复期患者的公共和私人TCR的结构，其与HLA-A2和两个SARS-CoV-2刺突蛋白表位（YLQ和RLQ）复合。这些结构揭示了由公共TCR而不是私有TCR选择特定TRAV和TRBV种系基因的基础，以及TCR识别RLQ而不是YLQ的天然变体的能力的基础。这两种TCR都不识别来自人类季节性冠状病毒的同源表位。通过阐明TCR识别免疫显性但可变表位（YLQ）和保守但不太常见的靶向表位（RLQ）的机制，这项研究可以为设计疫苗以引发泛冠状病毒免疫的前瞻性努力提供信息。结构免疫学对于理解免疫反应和感染因子之间的相互作用至关重要，但T细胞和SARS-CoV-2的研究落后于抗体和B细胞受体的研究。在这里，作者评估了公共和私人T细胞受体对SARS-CoV-2刺突表位及其天然变体的识别。
T cells play a vital role in combatting SARS-CoV-2 and forming long-term memory responses. Whereas extensive structural information is available on neutralizing antibodies against SARS-CoV-2, such information on SARS-CoV-2-specific T-cell receptors (TCRs) bound to their peptide–MHC targets is lacking. Here we determine the structures of a public and a private TCR from COVID-19 convalescent patients in complex with HLA-A2 and two SARS-CoV-2 spike protein epitopes (YLQ and RLQ). The structures reveal the basis for selection of particular TRAV and TRBV germline genes by the public but not the private TCR, and for the ability of the TCRs to recognize natural variants of RLQ but not YLQ. Neither TCR recognizes homologous epitopes from human seasonal coronaviruses. By elucidating the mechanism for TCR recognition of an immunodominant yet variable epitope (YLQ) and a conserved but less commonly targeted epitope (RLQ), this study can inform prospective efforts to design vaccines to elicit pan-coronavirus immunity. Structural immunology is critical in understanding the interplay between the immune response and the infective agent but such studies in T cells and SARS-CoV-2 lag behind those of antibodies and B-cell receptors. Here the authors assess recognition of SARS-CoV-2 spike epitopes and their natural variants by public and private T cell receptors.
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影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
影响因子：
32.4
作者：
Adams JJ;Narayanan S;Liu B;Birnbaum ME;Kruse AC;Bowerman NA;Chen W;Levin AM;Connolly JM;Zhu C;Kranz DM;Garcia KC
通讯作者：
Garcia KC
影响因子：
64.8
作者：
Alter G;Yu J;Liu J;Chandrashekar A;Borducchi EN;Tostanoski LH;McMahan K;Jacob-Dolan C;Martinez DR;Chang A;Anioke T;Lifton M;Nkolola J;Stephenson KE;Atyeo C;Shin S;Fields P;Kaplan I;Robins H;Amanat F;Krammer F;Baric RS;Le Gars M;Sadoff J;de Groot AM;Heerwegh D;Struyf F;Douoguih M;van Hoof J;Schuitemaker H;Barouch DH
通讯作者：
Barouch DH
影响因子：
10.7
作者：
Katoh K;Standley DM
通讯作者：
Standley DM
影响因子：
4.6
作者：
Clement M;Pearson JA;Gras S;van den Berg HA;Lissina A;Llewellyn-Lacey S;Willis MD;Dockree T;McLaren JE;Ekeruche-Makinde J;Gostick E;Robertson NP;Rossjohn J;Burrows SR;Price DA;Wong FS;Peakman M;Skowera A;Wooldridge L
通讯作者：
Wooldridge L