Predictions of immunogenicity reveal potent SARS-CoV-2 CD8+ T-cell epitopes

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Abstract

The recognition of pathogen or cancer-specific epitopes by CD8 + T cells is crucial for the clearance of infections and the response to cancer immunotherapy. This process requires epitopes to be presented on class I Human Leukocyte Antigen (HLA-I) molecules and recognized by the T-Cell Receptor (TCR). Machine learning models capturing these two aspects of immune recognition are key to improve epitope predictions. Here we assembled a high-quality dataset of naturally presented HLA-I ligands and experimentally verified neo-epitopes. We then integrated these data with new algorithmic developments to improve predictions of both antigen presentation and TCR recognition. Applying our tool to SARS-CoV-2 proteins enabled us to uncover several epitopes. TCR sequencing identified a monoclonal response in effector/memory CD8 + T cells against one of these epitopes and cross-reactivity with the homologous SARS-CoV-1 peptide.

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  1. SciScore for 10.1101/2022.05.23.492800: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    For the other three donors (Leu163, Leu158. Leu184), naive and effector/memory CD8+ T cells were isolated by Fluorescence-activated Cell Sorting (FACS) upon staining with anti-CD8 antibody (344710 BioLegend), anti-CCR7 antibody (353227 BioLegend) and anti-CD45RA antibody (304108 BioLegend) for 30 min at 4°C.
    Leu184
    suggested: None
    anti-CD8
    suggested: None
    anti-CCR7
    suggested: None
    anti-CD45RA
    suggested: (BioLegend Cat# 304108, RRID:AB_314412)
    ) fluorophore-conjugated anti-human antibodies.
    anti-human antibodies.
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    For TCR transfection, 1×106 Jurkat cells were co-electroporated with 3 μg of each TCR chain using a Neon Transfection System 100μl kit (Thermo Fisher Scientific) with the following parameters: 1325V, 10ms, 3 pulses.
    Jurkat
    suggested: None

    Results from OddPub: Thank you for sharing your code and 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.
    • 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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