SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8(+) T cell responses.
SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8(+) T cell responses.
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DOI：
10.1126/sciimmunol.abg6461
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发表时间：
2021-03-04
影响因子：
24.8
通讯作者：
Bergthaler A
中科院分区：
文献类型：
--
作者：
Agerer B;Koblischke M;Gudipati V;Montaño-Gutierrez LF;Smyth M;Popa A;Genger JW;Endler L;Florian DM;Mühlgrabner V;Graninger M;Aberle SW;Husa AM;Shaw LE;Lercher A;Gattinger P;Torralba-Gombau R;Trapin D;Penz T;Barreca D;Fae I;Wenda S;Traugott M;Walder G;Pickl WF;Thiel V;Allerberger F;Stockinger H;Puchhammer-Stöckl E;Weninger W;Fischer G;Hoepler W;Pawelka E;Zoufaly A;Valenta R;Bock C;Paster W;Geyeregger R;Farlik M;Halbritter F;Huppa JB;Aberle JH;Bergthaler A
通过深度病毒测序鉴定的MHC-I表位中的SARS-CoV-2突变通过减少肽-MHC-I结合来逃避CTL应答。CD 8 + T细胞对SARS-CoV-2的免疫与COVID-19的严重程度和病毒控制有关。在这里，我们在对747株SARS-CoV-2病毒分离株进行深度测序后，确定了MHC-I限制性CD 8 + T细胞表位的非同义突变。突变肽在无细胞体外试验中表现出减少或消除的MHC-I结合。突变肽的MHC-I结合减少与从HLA匹配的COVID-19患者中分离的CD 8 + T细胞的增殖、IFN-γ产生和细胞毒性活性降低相关。对来自COVID-19患者的离体扩增、四聚体分选的CD 8 + T细胞的单细胞RNA测序进一步揭示了对突变肽的转录应答的定性差异。我们的研究结果强调了SARS-CoV-2通过MHC-I限制性病毒表位的点突变破坏CD 8 + T细胞监视的能力。
SARS-CoV-2 mutations in MHC-I epitopes identified by deep viral sequencing evade CTL responses through decreased peptide-MHC-I binding. CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified nonsynonymous mutations in MHC-I-restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV-2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding in a cell-free in vitro assay. Reduced MHC-I binding of mutant peptides was associated with decreased proliferation, IFN-γ production and cytotoxic activity of CD8+ T cells isolated from HLA-matched COVID-19 patients. Single cell RNA sequencing of ex vivo expanded, tetramer-sorted CD8+ T cells from COVID-19 patients further revealed qualitative differences in the transcriptional response to mutant peptides. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through point mutations in MHC-I-restricted viral epitopes.
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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
DOI：
10.1084/jem.20050121
发表时间：
2005-06-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cox AL;Mosbruger T;Mao Q;Liu Z;Wang XH;Yang HC;Sidney J;Sette A;Pardoll D;Thomas DL;Ray SC
通讯作者：
Ray SC
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
64.8
作者：
Goulder, PJR;Brander, C;Walker, BD
通讯作者：
Walker, BD
影响因子：
56.9
作者：
Altman, JD;Moss, PAH;Davis, MM
通讯作者：
Davis, MM