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| Item Type: | Article |
|---|---|
| Title: | SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8(+) T cell responses |
| Creators Name: | Agerer, B., Koblischke, M., Gudipati, V., Montaño-Gutierrez, L.F., Smyth, M., Popa, A., Genger, J.W., Endler, L., Florian, D.M., Mühlgrabner, V., Graninger, M., Aberle, S.W., Husa, A.M., Shaw, L.E., Lercher, A., Gattinger, P., Torralba-Gombau, R., Trapin, D., Penz, T., Barreca, D., Fae, I., Wenda, S., Traugott, M., Walder, G., Pickl, W.F., 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, J.B., Aberle, J.H. and Bergthaler, A. |
| Abstract: | 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. |
| Keywords: | CD8-Positive T-Lymphocytes, COVID-19, Cell Proliferation, T-Lymphocyte Epitopes, HLA-A Antigens, High-Throughput Nucleotide Sequencing, Cellular Immunity, Interferon-gamma, Mutation, Peptides, SARS-CoV-2, SARS-CoV-2 / Immunology |
| Source: | Science Immunology |
| ISSN: | 2470-9468 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 6 |
| Number: | 57 |
| Page Range: | eabg6461 |
| Date: | March 2021 |
| Official Publication: | https://doi.org/10.1126/sciimmunol.abg6461 |
| PubMed: | View item in PubMed |
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