1. Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis
- Author
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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, and Xun Lan
- Subjects
Biology (General) ,QH301-705.5 - Abstract
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.
- Published
- 2024
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