Frontiers in Immunology (May 2023)

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

DOI
https://doi.org/10.3389/fimmu.2023.1130876
Journal volume & issue
Vol. 14

Abstract

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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.

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