Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07048-x |
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| author | 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 |
| author_facet | 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 |
| author_sort | Lihui Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-aaf1faa28e9d45c0adb8c6cfafefb907 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-aaf1faa28e9d45c0adb8c6cfafefb9072024-11-10T12:39:07ZengNature PortfolioCommunications Biology2399-36422024-11-017111210.1038/s42003-024-07048-xIdentification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesisLihui Wang0Runda Xu1Daosheng Huang2Pai Peng3Keyong Sun4Jie Hu5Bei-zhong Liu6Liang Fang7Liwen Zhang8Xin Sun9Fei Gu10Ni Tang11Ai-long Huang12Xin Lin13Xun Lan14Department of Basic Medical Science, School of Medicine, Tsinghua UniversityDepartment of Basic Medical Science, School of Medicine, Tsinghua UniversityDepartment of Basic Medical Science, School of Medicine, Tsinghua UniversityKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical UniversityDepartment of Basic Medical Science, School of Medicine, Tsinghua UniversityKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical UniversityYong-Chuan Hospital of Chongqing Medical UniversityYong-Chuan Hospital of Chongqing Medical UniversityDepartment of Basic Medical Science, School of Medicine, Tsinghua UniversityDepartment of Basic Medical Science, School of Medicine, Tsinghua UniversityAlibaba GroupKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical UniversityKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical UniversityDepartment of Basic Medical Science, School of Medicine, Tsinghua UniversityDepartment of Basic Medical Science, School of Medicine, Tsinghua UniversityAbstract 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.https://doi.org/10.1038/s42003-024-07048-x |
| spellingShingle | 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 Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis Communications Biology |
| title | Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis |
| title_full | Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis |
| title_fullStr | Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis |
| title_full_unstemmed | Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis |
| title_short | Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis |
| title_sort | identification of virus epitopes and reactive t cell receptors from memory t cells without peptide synthesis |
| url | https://doi.org/10.1038/s42003-024-07048-x |
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