SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes [10x]

CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified non-synonymous 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, which was associated with a loss of recognition and functional responses by CD8+ T cells isolated from HLA-matched COVID-19 patients. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through sporadically emerging escape mutations in MHC- I restricted viral epitopes.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001006995	The data contains single-cell gene sequencing data (10x Genomics) from FACS-purified CD8 T lymphocytes from two Austrian patients. The cells were stimulated with one MHC class I peptides obtained from a common (wild type) variant and an emerging mutant variant of the SARS-Cov-2 virus. Then the samples were multiplexed using hashtag oligos. We provide the raw and aligned sequence data for: i. The single-cell experiments ii. The PCR-amplified samples for enrichment of the hashtag oligo multiplexing barcodes iii. The PCR-amplified samples for enrichment of the T Cell Receptor (TCR) VDJ region for immuno-profiling. The samples and libraries were processed and obtained in collaboration between St. Anna Children's Cancer Research Institute (CCRI), CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, and the Medical University of Vienna. The cell barcodes and processed data has been submitted to the GEO database with GEO accession GSE166651.	Illumina NovaSeq 6000	2
EGAD00001008109	Full information about the T cell receptor (CR) variable regions found in the sequences of the vdj region. Columns: barcode is_cell contig_id high_confidence length chain v_gene d_gene j_gene c_gene full_length productive cdr3 cdr3_nt reads umis raw_clonotype_id raw_consensus_id		2

Publications	Citations
SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses. 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. Sci Immunol 6: 2021 eabg6461	105

Publications

Citations

SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses.
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. Sci Immunol 6: 2021 eabg6461

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