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| Status |
Public on Mar 25, 2021 |
| Title |
Identification and characterization of a SARS-CoV-2 specific CD8 T cell response with immunodominant features |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The COVID-19 pandemic caused by SARS-CoV-2 is a continuous challenge worldwide, and there is an urgent need to map the landscape of immunogenic and immunodominant epitopes recognized by CD8 T cells. Here, we analyze samples from 31 COVID-19 patients for CD8 T cell recognition of 500 peptide-HLA class I complexes, restricted by 10 common HLA alleles. We identify 18 CD8 T cell recognized SARS-CoV-2 epitopes, including an epitope with immunodominant features derived from ORF1ab and restricted by HLA-A*01:01. In-depth characterization of SARS-CoV-2-specific CD8 T cell responses of patients with acute critical and severe disease reveals high expression of NKG2A, lack of cytokine production and a gene expression profile inhibiting T cell re-activation and migration while sustaining survival. SARS-CoV-2-specific CD8 T cell responses are detectable up to 5 months post recovery from critical and severe disease, and these responses convert from dysfunctional effector to functional memory CD8 T cells during convalescence.
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| Overall design |
Single-cell RNA sequencing (incl. TCRseq) using the 10x Genomics Chromium system (5' kit) was performed on CD8 T cells from 6 COVID-19 patients with acute severe and critical disease. Bulk CD8 T cells were sorted from PBMCs and sequenced in two independent experiments (batch I and II). Patients were hashtagged (BioLegend TotalSeq-C anti-human hashtags) and pMHC monomers with indicated epitopes were conjugated to TotalSeq-C-conjugated-streptavidin. Barcode/hashtag assignments (batch I): Patient COVID-087 (Hashtag #1: GTCAACTCTTTAGCG); Epitopes: RLNEVAKNL-MHC (CGTATGCGCTTCAAG), YLQPRTFLL-MHC (CAGCAACTTCATTGT). Patient COVID-096 (Hashtag #3: TTCCGCCTCTCTTTG); Epitopes: PTDNYITTY-MHC (CAGCAACTTCATTGT), TTDPSFLGRY-MHC (GGTATAAGAGCTACG), TVATSRTLSY-MHC (ATGCGATCAGACCGA). Patient COVID-117 (Hashtag #4: AGTAAGTTCAGCGTA); Epitopes: TTDPSFLGRY-MHC (GGTATAAGAGCTACG). Patient COVID-143 (Hashtag #5: AAGTATCGTTTCGCA); Epitopes: CTDDNALAYY-MHC (ATGCGATCAGACCGA), DTDFVNEFY-MHC (CGTATGCGCTTCAAG), PTDNYITTY-MHC (CAGCAACTTCATTGT), TTDPSFLGRY-MHC (GGTATAAGAGCTACG). Patient COVID-153 (Hashtag #7: TGTCTTTCCTGCCAG); Epitopes: PTDNYITTY-MHC (CAGCAACTTCATTGT), TTDPSFLGRY-MHC (GGTATAAGAGCTACG). Barcode/hashtag assignments (batch II): Patient COVID-131 (Hashtag #1: GTCAACTCTTTAGCG), TTDPSFLGRY-MHC (ATGCGATCAGACCGA), VTEHDTLLY-MHC (CGTATGCGCTTCAAG), PTDNYITTY-MHC (CAGCAACTTCATTGT), FTSDYYQLY-MHC (GGTATAAGAGCTACG)
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| Contributor(s) |
Gangaev A, Ketelaars SL, Isaeva OI, Patiwael S, Dopler A, Hoefakker K, De Biasi S, Gibellini L, Mussini C, Guaraldi G, Girardis M, Talavera Ormeno CM, Hekking PJ, Lardy NM, Toebes M, Balderas R, Schumacher TN, Ovaa H, Cossarizza A, Kvistborg P |
| Citation(s) |
33972535 |
| Submission date |
Mar 24, 2021 |
| Last update date |
Jul 15, 2021 |
| Contact name |
Pia Kvistborg |
| E-mail(s) |
p.kvistborg@nki.nl
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| Organization name |
Netherlands Cancer Institute
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| Department |
Molecular Oncology & Immunology
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| Street address |
Plesmanlaan 121
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| City |
Amsterdam |
| State/province |
FOREIGN |
| ZIP/Postal code |
1066CX |
| Country |
Netherlands |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA716830 |
| SRA |
SRP311934 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE169503_RAW.tar |
25.9 Mb |
(http)(custom) |
TAR (of CSV, MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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