Clonal diversity determines persistence of SARS-CoV-2 epitope-specific T cell response
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Abstract
T cells play a pivotal role in reducing disease severity during SARS-CoV-2 infection and formation of long-term immune memory. We studied 50 COVID-19 convalescent patients and found that T cell response was induced more frequently and persisted longer than circulating antibodies. To identify epitopes that give rise to long-lived T cell memory, we performed ex vivo T cell expansion, MHC-tetramer cell-sorting, and high-throughput sequencing. We identified 756 clonotypes specific to nine known CD8 + T cell receptor (TCR) epitopes. Some epitopes were recognized by highly similar public clonotypes with restricted variable and joining segment usage. Receptors for other epitopes were extremely diverse, suggesting alternative modes of recognition. We also tracked persistence of epitope-specific response and individual clonotypes for a median of eight months after infection. The number of recognized epitopes per patient and quantity of epitope-specific clonotypes decreased over time, but the studied epitopes were characterized by uneven decline in the number of specific T cells. Epitopes with more clonally diverse TCR repertoires induced more pronounced and durable responses. In contrast, the abundance of specific clonotypes in peripheral circulation had no influence on their persistence. Our study demonstrates the durability of SARS-CoV-2-specific CD8 + memory, and offers important implications for vaccine design.
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SciScore for 10.1101/2022.04.18.22273961: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All donors signed the informed consent form approved by the National Research Center for Hematology ethical committee (N 150, 02.07.2020) before enrollment.
IACUC: All donors signed the informed consent form approved by the National Research Center for Hematology ethical committee (N 150, 02.07.2020) before enrollment.
IRB: Additionally, 19 healthy donor (HD) samples were obtained: 14 from the National Medical Research Center for Hematology blood bank (cryopreserved no later than August 2019) with the approval of the local ethical committee, and 5 recruited during the COVID-19 pandemic with no self-reported symptoms and negative PCR test results (four of them subsequently became …SciScore for 10.1101/2022.04.18.22273961: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All donors signed the informed consent form approved by the National Research Center for Hematology ethical committee (N 150, 02.07.2020) before enrollment.
IACUC: All donors signed the informed consent form approved by the National Research Center for Hematology ethical committee (N 150, 02.07.2020) before enrollment.
IRB: Additionally, 19 healthy donor (HD) samples were obtained: 14 from the National Medical Research Center for Hematology blood bank (cryopreserved no later than August 2019) with the approval of the local ethical committee, and 5 recruited during the COVID-19 pandemic with no self-reported symptoms and negative PCR test results (four of them subsequently became infected, and their post-infection samples were included in CP cohort).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources An Aria III cell sorter (BD Biosciences) was used to sort cells, and data were analyzed using FlowJo Software (version 10.6.1) . FlowJosuggested: (FlowJo, RRID:SCR_008520)Spots were counted by CTL ImmunoSpot Analyzer using ImmunoSpot software. ImmunoSpotsuggested: NoneTCR repertoire data were analyzed using MIXCR, MIGEC, and VDJtools software with default settings. VDJtoolssuggested: NoneQuantification and Statistical Analysis: All data comparisons were performed using GraphPad Prism 8 software and python3. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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