Expression profiling by high throughput sequencing Other
Summary
Effective presentation of antigens by HLA class I molecules to CD8+ T cells is required for viral elimination and generation of long-term immunological memory. In this study, we applied a single-cell, multi-omic technology to generate the first unified ex vivo characterization of the CD8+ T cell response to SARS-CoV-2 across 4 major HLA class I alleles. We found that HLA genotype conditions key features of epitope specificity, TCR a/b sequence diversity, and the utilization of pre-existing SARS-CoV-2 reactive memory T cell pools. Single-cell transcriptomics revealed functionally diverse T cell phenotypes of SARS-CoV-2-reactive T cells, associated with both disease stage and epitope specificity. Our results show that HLA variations significantly influence the CD8+ T cell repertoire shape and utilization of immune recall upon SARS-CoV-2 infection.
Overall design
We performed analysis of CD8+ T cell responses in PBMCs from three cohorts - acute COVID, convalesecent COVID, and unexposed subjects. Single-cell sequencing was used for quantification of mRNA expression, tetramer binding, and ADT binding. Some samples were multiplexed with cell hashing. The metadata and hashtog barcode oligo sequence for each hashed sample is included in the file GEO_upload_seq_CIPHER_2021_11_04_Supplemental_Sample_to_HTO.xlsx, available at the foot of this record.
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