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

Anna Postovskaya, Alexandra Vujkovic, Tessa de Block, Lida van Petersen, Maartje van Frankenhuijsen, Isabel Brosius, Emmanuel Bottieau, Christophe Van Dijck, Caroline Theunissen, Sabrina H van Ierssel, Erika Vlieghe, Esther Bartholomeus, Kerry Mullan, Wim Adriaensen, Guido Vanham, Benson Ogunjimi, Kris Laukens, Koen Vercauteren, Pieter Meysman

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Despite the general agreement on the significance of T cells during SARS-CoV-2 infection, the clinical impact of specific and cross-reactive T-cell responses remains uncertain. Understanding this aspect could provide insights for adjusting vaccines and maintaining robust long-term protection against continuously emerging variants. To characterize CD8+ T-cell response to SARS-CoV-2 epitopes unique to the virus (SC2-unique) or shared with other coronaviruses (CoV-common), we trained a large number of T-cell receptor (TCR) - epitope recognition models for MHC-I-presented SARS-CoV-2 epitopes from publicly available data. These models were then applied to longitudinal CD8+ TCR repertoires from critical and non-critical COVID-19 patients. In spite of comparable initial CoV-common TCR repertoire depth and CD8+ T-cell depletion, the temporal dynamics of SC2-unique TCRs differed depending on the disease severity. Specifically, while non-critical patients demonstrated a large and diverse SC2-unique TCR repertoire by the second week of the disease, critical patients did not. Furthermore, only non-critical patients exhibited redundancy in the CD8+ T-cell response to both groups of epitopes, SC2-unique and CoV-common. These findings indicate a valuable contribution of the SC2-unique CD8+ TCR repertoires. Therefore, a combination of specific and cross-reactive CD8+ T-cell responses may offer a stronger clinical advantage. Besides tracking the specific and cross-reactive SARS-CoV-2 CD8+ T cells in any TCR repertoire, our analytical framework can be expanded to more epitopes and assist in the assessment and monitoring of CD8+ T-cell response to other infections.

Original languageEnglish
Article number1130876
JournalFrontiers in Immunology
Number of pages14
Publication statusPublished - 2023


  • Humans
  • SARS-CoV-2
  • COVID-19
  • Epitopes, T-Lymphocyte
  • Receptors, Antigen, T-Cell
  • CD8-Positive T-Lymphocytes


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