Analysis of SARS-CoV-2 specific T-cell receptors in ImmuneCode reveals cross-reactivity to immunodominant Influenza M1 epitope

  1. John-William Sidhom
  2. Alexander S. Baras

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Adaptive Biotechnologies and Microsoft have recently partnered to release ImmuneCode, a database containing SARS-CoV-2 specific T-cell receptors derived through MIRA, a T-cell receptor (TCR) sequencing based sequencing approach to identify antigen-specific TCRs. Herein, we query the extent of cross reactivity between these derived SARS-CoV-2 specific TCRs and other known antigens present in McPas-TCR, a manually curated catalogue of pathology-associated TCRs. We reveal cross reactivity between SARS-CoV-2 specific TCRs and the immunodominant Influenza GILGFVFTL M1 epitope, suggesting the importance of further work in characterizing the implications of prior Influenza exposure or co-exposure to the pathology of SARS-CoV-2 illness.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.06.20.160499: (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

    No key resources detected.

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

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    However, there are several limitations of this study. The number of individuals in this study was fairly small with 7 exposed and 5 non-exposed individuals. Given the lack of power in this analysis, it was difficult to assess for any differences in the extent of cross reactivity in exposed vs non-exposed individuals. Differences in cross reactivity may shed light on the role of Influenza specific antigen-experienced T-cells in the control of SARS-CoV-2 infection. Furthermore, given these results, future studies may want to consider comparing the clinical course in Influenza vaccinated vs unvaccinated individuals. Another significant limitation is assessing the certainty of antigen-specificity of a given TCR. Often, specificity of a TCR is determined in a high throughput fashion through methods such as tetramer sorting or T-cell expansion based assays, which can be inherently noisy and non-specific sources of data (Sidhom et al., n.d.). This problem is highlighted in Figure 1A when we compare the distribution of unique TCR sequences in the McPAS-TCR database vs the sampled distribution of SARS-CoV-2 specific TCRs. While there is clear enrichment in the M1 epitope, the NP 177 epitope, while demonstrating a large number of TCRs that are seemingly cross-reactive, the enrichment over the background distribution within McPas-TCR is not significant, suggesting that this may be nonspecific signal within the MIRA assay. In light of these limitations, T-cell recognition assays such as ...

    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.

  2. Version published to 10.1101/2020.06.20.160499v1 on bioRxiv