Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2

  1. Jun Siong Low
  2. Daniela Vaqueirinho
  3. Federico Mele
  4. Mathilde Foglierini
  5. Josipa Jerak
  6. Michela Perotti
  7. David Jarrossay
  8. Sandra Jovic
  9. Laurent Perez
  10. Rosalia Cacciatore
  11. Tatiana Terrot
  12. Alessandra Franzetti Pellanda
  13. Maira Biggiogero
  14. Christian Garzoni
  15. Paolo Ferrari
  16. Alessandro Ceschi
  17. Antonio Lanzavecchia
  18. Federica Sallusto
  19. Antonino Cassotta

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Abstract

A better understanding of CD4 + T cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to the design of effective next-generation vaccines. Low et al. defined and estimated the CD4 + T cell repertoire of convalescent COVID-19 patients. After sorting various CD4 + T cell subsets, they generated numerous T cell clones that reacted to the SARS-CoV-2 spike protein. A large number of T cell clones from almost all individuals recognized a small conserved immunodominant region within the spike protein receptor-binding domain (RBD). The researchers isolated T cell clones that broadly reacted to the spike protein of other coronaviruses, providing evidence for the recall of preexisting cross-reactive memory T cells after SARS-CoV-2 infection.

Science , abg8985, this issue p. 1336

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  1. Version published to 10.1126/science.abg8985
  2. ScreenIT

    SciScore for 10.1101/2021.03.23.436642: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study protocol was approved by the Cantonal Ethics Committee of Ticino, Switzerland (CE-TI-3428, 2018-02166).
    Consent: All blood donors provided written informed consent for participation in the study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    After washing, cells were stained with PE/Cy7-Streptavidin (cat. no. 405206) from BioLegend, and with the following fluorochrome-labeled mouse monoclonal antibodies: CD8-PE-Cy5 (clone B9.11; cat. no. A07758), CD56-PE/Cy5 (clone N901; cat. no. A07789) from Beckman Coulter, CD25-PE (clone M-A251; cat. no. 555432) from BD Biosciences,
    CD25-PE
    suggested: (BD Biosciences Cat# 555432, RRID:AB_395826)
    To determine HLA restriction, T cell clones were stimulated with autologous APCs pulsed with SARS-CoV-2 Spike peptides, in the absence or presence of blocking anti-class II monoclonal antibodies produced in house from hybridoma cell lines (anti-HLA-DR, clone L243 from ATCC, cat. no. HB-55; anti-HLA-DQ, clone SPVL3 (27); anti-HLA-DP, clone B7/21 (28), anti-pan-MHC-class-II, clone IVA12 from ATCC, cat. no. HB-145).
    anti-class II
    suggested: None
    anti-HLA-DR
    suggested: None
    anti-HLA-DQ
    suggested: None
    anti-HLA-DP
    suggested: None
    anti-pan-MHC-class-II
    suggested: None
    Software and Algorithms
    SentencesResources
    Conservation analysis: Accession numbers of Spike protein sequences used for S346-365 conservation analysis are: SARS-CoV-2 Wuhan-Hu-1/2019 (GenBank: NC_045512.2) ; SARS-CoV-2 B.1.1.7 (GISAID: EPI_ISL_700654); SARS-CoV-2 B.1.351 (GISAID: EPI_ISL_700492); SARS-CoV-2 P.1 (GISAID: EPI_ISL_833137); Bat-CoV-RaTG13 (GenBank: QHR63300.2); GD Pangolin (GISAID: EPI_ISL_410721; 471470; 471469; 471468;
    Conservation
    suggested: (Conservation, RRID:SCR_016064)
    Bat CoV WIV1 (GenBank:
    GenBank
    suggested: (GenBank, RRID:SCR_002760)
    Statistical analysis: Statistical analyses were performed using GraphPad Prism 8 software.
    GraphPad Prism
    suggested: (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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.03.23.436642 on bioRxiv