SARS-CoV-2 variant B.1.1.7 caused HLA-A2 + CD8 + T cell epitope mutations for impaired cellular immune response

  1. Chanchan Xiao
  2. Lipeng Mao
  3. Zhigang Wang
  4. Guodong Zhu
  5. Lijuan Gao
  6. Jun Su
  7. Xiongfei Chen
  8. Jun Yuan
  9. Yutian Hu
  10. Zhinan Yin
  11. Jun Xie
  12. Weiqing Ji
  13. Haitao Niu
  14. Feng Gao
  15. Oscar Junhong Luo
  16. Lianbo Xiao
  17. Pengcheng Wang
  18. Guobing Chen

Reviewed by

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

Log in to save this article

Abstract

The rapid spreading of the newly emerged SARS-CoV-2 variant, B.1.1.7, highlighted the requirements to better understand adaptive immune responses to this virus. Since CD8 + T cell responses play an important role in disease resolution and modulation in COVID-19 patients, it is essential to address whether these newly emerged mutations would result in altered immune responses. Here we evaluated the immune properties of the HLA-A2 restricted CD8 + T cell epitopes containing mutations from B.1.1.7, and furthermore performed a comprehensive analysis of the SARS-CoV-2 specific CD8 + T cell responses from COVID-19 convalescent patients and SARS-CoV-2 vaccinees recognizing the ancestral Wuhan strain compared to B.1.1.7. First, most of the predicted CD8 + T cell epitopes showed proper binding with HLA-A2, while epitopes from B.1.1.7 had lower binding capability than those from the ancestral strain. In addition, these peptides could effectively induced the activation and cytotoxicity of CD8 + T cells. Our results further showed that at least two site mutations in B.1.1.7 resulted in a decrease in CD8 + T cell activation and a possible immune evasion, namely A1708D mutation in ORF1ab 1707-1716 and I2230T mutation in ORF1ab 2230-2238 . Our current analysis provides information that contributes to the understanding of SARS-CoV-2-specific CD8 + T cell responses elicited by infection of mutated strains or vaccination.

Graphical Abstract

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.03.28.437363: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Human subjects: The Institutional Review Board of the Affiliated Huaqiao Hospital of Jinan University approved this study.
    Consent: All subjects provided informed consent at the time of enrollment that their samples could be used for this study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Cells were stained with PE anti-human HLA-A2 antibody (BioLegend) at 4 °C in the dark for 30 min, and acquired in flow cytometer FACS Canto (BD).
    anti-human HLA-A2
    suggested: None
    HLA-A2 positive PBMC samples were further stained with PE labeled tetramer (home-made), PerCP labeled human CD8+ antibody (BioLegend), APC labeled human CCR7 antibody (BioLegend), FITC labeled human CD45RA antibody (BioLegend) and acquired with flow cytometer FACS Canto (BD).
    human CD8+
    suggested: None
    human CCR7
    suggested: None
    human CD45RA
    suggested: None
    0.5 × 106 CD8+ T cells isolated from health donors were co-cultured with 0.5 × 106 peptide-loaded T2A2 cells stained with 5 μmol/L CFSE (TargetMol), and stimulated with 1 μg/mL anti-human CD28 antibodies (BioLegend) and 50 IU/mL IL-2 (SL PHARM, Recombinant Human Interleukin-2(125Ala) Injection).
    anti-human CD28
    suggested: None
    Software and Algorithms
    SentencesResources
    PyMol 1.1 software was used to calculate the angle deflection of benzene ring in the polypeptide, and used the central atoms of three amino acids to calculate the angle.
    PyMol
    suggested: (PyMOL, RRID:SCR_000305)
    Statistical Analysis: The data were analyzed by one-way ANOVA and paired-samples t-tests for statistical significance by using Graphpad prism 8 and SPSS 22.0 software.
    Graphpad
    suggested: (GraphPad, RRID:SCR_000306)
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: Thank you for sharing your data.

    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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 25 and 27. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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.

  2. Version published to 10.1101/2021.03.28.437363 on bioRxiv