Communications Biology (Nov 2024)

Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis

  • Lihui Wang,
  • Runda Xu,
  • Daosheng Huang,
  • Pai Peng,
  • Keyong Sun,
  • Jie Hu,
  • Bei-zhong Liu,
  • Liang Fang,
  • Liwen Zhang,
  • Xin Sun,
  • Fei Gu,
  • Ni Tang,
  • Ai-long Huang,
  • Xin Lin,
  • Xun Lan

DOI
https://doi.org/10.1038/s42003-024-07048-x
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 12

Abstract

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Abstract Identifying epitopes and their corresponding T-cell receptor (TCR) sequences is crucial in the face of rapidly mutating viruses. Peptide synthesis is often required to confirm the exact epitope sequences, which is time-consuming and expensive. In this study, we introduce a scalable workflow to identify the exact sequences of virus epitopes and reactive TCRs targeting the epitopes from memory T cells. Following the narrowing down of epitopes to specific regions via the tandem minigene (TMG) system, our workflow incorporates the utilization of peptide-major histocompatibility complex-displaying yeasts (pMHC-displaying yeasts) to rapidly screen immunogenic epitopes’ precise sequences, obviating the necessity for the chemical synthesis of peptides. Focusing on SARS-CoV-2, we identify the precise sequences of reactive TCRs, targeting conserved epitopes across the Coronaviridae family, from the blood of COVID-19-recovered individuals over 8 months. Notably, we reveal that at least 75% (6/8) of the tested donors harbor T cells targeting a shared epitope, KTFPPTEPK, derived from the N protein. Furthermore, several identified TCRs exhibit cross-reactivity to mutant epitopes, suggesting a potential mechanism for sustained T-cell responses against emerging SARS-CoV-2 variants.