دورية أكاديمية
SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses.
| العنوان: | SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses. |
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| المؤلفون: | Agerer, Benedikt, Koblischke, Maximilian, Gudipati, Venugopal, Montaño-Gutierrez, Luis Fernando, Smyth, Mark, Popa, Alexandra, Genger, Jakob-Wendelin, Endler, Lukas, Florian, David M., Mühlgrabner, Vanessa, Graninger, Marianne, Aberle, Stephan W., Husa, Anna-Maria, Shaw, Lisa Ellen, Lercher, Alexander, Gattinger, Pia, Torralba-Gombau, Ricard, Trapin, Doris, Penz, Thomas, Barreca, Daniele |
| المصدر: | Science Immunology; 2021, Vol. 6 Issue 57, p1-12, 12p |
| مستخلص: | 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: | Complementary Index |
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