Article Synopsis
- Researchers are exploring T cells that react to SARS-CoV-2 to better understand their characteristics and functions.
- By using single-cell RNA sequencing and reverse phenotyping, the study identifies and profiles these T cells from COVID-19 patients without heavily relying on traditional methods.
- The findings reveal differences in transcriptional signatures of activated T cells and their impact on T cells found in the respiratory tract of patients, highlighting the utility of reverse phenotyping in studying T cell responses across different conditions.
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Article Abstract
The in vivo phenotypic profile of T cells reactive to severe acute respiratory syndrome (SARS)-CoV-2 antigens remains poorly understood. Conventional methods to detect antigen-reactive T cells require in vitro antigenic re-stimulation or highly individualized peptide-human leukocyte antigen (pHLA) multimers. Here, we use single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from Coronavirus Disease 2019 (COVID-19) patients. To do so, we induce transcriptional shifts by antigenic stimulation in vitro and take advantage of natural T cell receptor (TCR) sequences of clonally expanded T cells as barcodes for 'reverse phenotyping'. This allows identification of SARS-CoV-2-reactive TCRs and reveals phenotypic effects introduced by antigen-specific stimulation. We characterize transcriptional signatures of currently and previously activated SARS-CoV-2-reactive T cells, and show correspondence with phenotypes of T cells from the respiratory tract of patients with severe disease in the presence or absence of virus in independent cohorts. Reverse phenotyping is a powerful tool to provide an integrated insight into cellular states of SARS-CoV-2-reactive T cells across tissues and activation states.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313584 | PMC |
| http://dx.doi.org/10.1038/s41467-021-24730-4 | DOI Listing |
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