Leveraging T-cell receptor – epitope recognition models to disentangle unique and cross-reactive T-cell response to SARS-CoV-2 during COVID-19 progression/resolution

  1. Anna Postovskaya
  2. Alexandra Vujkovic
  3. Tessa de Block
  4. Lida van Petersen
  5. Maartje van Frankenhuijsen
  6. Isabel Brosius
  7. Emmanuel Bottieau
  8. Christophe Van Dijck
  9. Caroline Theunissen
  10. Sabrina H. van Ierssel
  11. Erika Vlieghe
  12. Esther Bartholomeus
  13. Wim Adriaensen
  14. Guido Vanham
  15. Benson Ogunjimi
  16. Kris Laukens
  17. Koen Vercauteren
  18. Pieter Meysman

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Abstract

Despite the general agreement on the importance of T cells during SARS-CoV-2 infection, the clinical impact of specific and cross-reactive T-cell responses remains uncertain, while this knowledge may indicate how to adjust vaccines and maintain robust long-term protection against continuously emerging variants. To characterize CD8+ T-cell response to epitopes unique to SARS-CoV-2 (SC-unique) or shared with other coronaviruses (CoV-common), we trained a large number of TCR-epitope recognition models for MHC-I-presented SARS-CoV-2 epitopes from publicly available data. Applying those models to longitudinal COVID-19 TCR repertoires of critical and non-critical COVID-19 patients, we discovered that notwithstanding comparable CD8+ T-cell depletion and the sizes of putative CoV-common CD8+ TCR repertoires in all symptomatic patients at the initial stage of the disease, the temporal dynamics of putative SC2-unique TCRs differed depending on the disease severity. Only non-critical patients had developed large and diverse SC2-unique CD8+ T-cell response by the second week of the disease. Additionally, only this patient group demonstrated redundancy in CD8+ TCRs putatively recognizing unique and common SARS-CoV-2 epitopes. Our findings thus emphasize the role of the de novo CD8+ T-cell response and support the argument against the clinical benefit of pre-existing cross-reactive CD8+ T cells. Now, the analytical framework of this study can not only be employed to track specific and cross-reactive SARS-CoV-2 CD8+ T cells in any TCR repertoire but also be generalized to more epitopes and be employed for adaptive immune response assessment and monitoring to inform public health decisions.

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    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Sequence identity between proteins was established using a pairwise protein BLAST.
    BLAST
    suggested: (BLASTX, RRID:SCR_001653)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

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    Results from JetFighter: We did not find any issues relating to colormaps.

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    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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  2. Version published to 10.1101/2020.09.09.289355 on bioRxiv