CD8 T cell epitope generation toward the continually mutating SARS-CoV-2 spike protein in genetically diverse human population: Implications for disease control and prevention

  1. Elisa Guo
  2. Hailong Guo

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

The ongoing pandemic of SARS-CoV-2 has brought tremendous crisis on global health care systems and industrial operations that dramatically affect the economic and social life of numerous individuals worldwide. Understanding anti-SARS-CoV-2 immune responses in population with different genetic backgrounds and tracking the viral evolution are crucial for successful vaccine design. In this study, we reported the generation of CD8 T cell epitopes by a total of 80 alleles of three major class I HLAs using NetMHC 4.0 algorithm for the SARS-CoV-2 spike protein, which can be targeted by both B cells and T cells. We found diverse capacities of S protein specific epitope presentation by different HLA alleles with very limited number of predicted epitopes for HLA-B*2705, HLA-B*4402 and HLA-B*4403 and as high as 132 epitopes for HLA-A*6601. Our analysis of 1000 S protein sequences from field isolates collected globally over the past few months identified three recurrent point mutations including L5F, D614G and G1124V. Differential effects of these mutations on CD8 T cell epitope generation by corresponding HLA alleles were observed. Finally, our multiple alignment analysis indicated the absence of seasonal CoV induced cross-reactive CD8 T cells to drive these mutations. Our findings suggested that individuals with certain HLA alleles, such as B*44 are more prone to SARS-CoV-2 infection. Studying anti-S protein specific CD8 T cell immunity in diverse genetic background is critical for better control and prevention of the SARS-CoV-2 pandemic.

Article activity feed

  1. Version published to 10.1371/journal.pone.0239566
  2. ScreenIT

    SciScore for 10.1101/2020.09.10.290841: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    These sequences were deposited in the NCBI database with collection dates ranging from January to June 2020 and showed at least 95% of query coverage for the reference S protein (accession number QHD43416.1).
    NCBI
    suggested: (NCBI, RRID:SCR_006472)
    Multiple alignment of these 1000 protein sequences against the reference S protein was conducted using NCBI BLASTP program under default conditions.
    BLASTP
    suggested: (BLASTP, RRID:SCR_001010)
    Comparison of CoV S protein sequences: The S protein sequences of four common seasonal CoVs: HCoV-229E (AAG48592.1), HCoV-OC43 (CAA83661.1), HCoV-NL63 (APF29063.1), and HCoV-HKU1 (BBA20983.1) were used for comparison with the reference S protein of SARS-CoV 2 by multiple alignment in MEGA-X using MUSCLE under default conditions.
    MUSCLE
    suggested: (MUSCLE, RRID:SCR_011812)

    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: 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.
    • No funding statement was detected.
    • 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 10.1101/2020.09.10.290841v1 on bioRxiv