Analysis of SARS-CoV-2 specific T-cell receptors in ImmuneCode reveals cross-reactivity to immunodominant Influenza M1 epitope
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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.
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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 Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not 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. …
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 Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not 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.
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