Identification of SARS-CoV-2-specific T cell and its receptor
© 2024. The Author(s)..
The T-cell receptor (TCR) repertoires exhibits distinct signatures associated with COVID-19 severity. However, the precise identification of vaccine-induced SARS-CoV-2-specific TCRs and T-cell immunity mechanisms are unknown. We developed a machine-learning model that can differentiate COVID-19 patients from healthy individuals based on TCR sequence features with an accuracy of 95.7%. Additionally, we identified SARS-CoV-2-specific T cells and TCR in HLA-A*02 vaccinated individuals by peptide stimulation. The SARS-CoV-2-specific T cells exhibited higher cytotoxicity and prolonged survival when targeting spike-pulsed cells in vitro or in vivo. The top-performing TCR was further tested for its affinity and cytotoxic effect against SARS-CoV-2-associated epitopes. Furthermore, single-cell RNA sequencing (scRNA-seq), immune repertoire sequencing (IR-seq) and flow cytometry were used to access vaccine-induced cellular immunity, which demonstrated that robust T cell responses (T cell activation, tissue-resident memory T cell (Trm) generation, and TCR clonal expansion) could be induced by intranasal vaccination. In summary, we identified the SARS-CoV-2-associated TCR repertoires profile, specific TCRs and T cell responses. This study provides a theoretical basis for developing effective immunization strategies.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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Enthalten in: |
Journal of hematology & oncology - 17(2024), 1 vom: 27. März, Seite 15 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Zhang, Qian [VerfasserIn] |
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Links: |
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Themen: |
Immune repertoire |
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Anmerkungen: |
Date Completed 29.03.2024 Date Revised 19.04.2024 published: Electronic Citation Status MEDLINE |
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doi: |
10.1186/s13045-024-01537-6 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM370288203 |
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520 | |a The T-cell receptor (TCR) repertoires exhibits distinct signatures associated with COVID-19 severity. However, the precise identification of vaccine-induced SARS-CoV-2-specific TCRs and T-cell immunity mechanisms are unknown. We developed a machine-learning model that can differentiate COVID-19 patients from healthy individuals based on TCR sequence features with an accuracy of 95.7%. Additionally, we identified SARS-CoV-2-specific T cells and TCR in HLA-A*02 vaccinated individuals by peptide stimulation. The SARS-CoV-2-specific T cells exhibited higher cytotoxicity and prolonged survival when targeting spike-pulsed cells in vitro or in vivo. The top-performing TCR was further tested for its affinity and cytotoxic effect against SARS-CoV-2-associated epitopes. Furthermore, single-cell RNA sequencing (scRNA-seq), immune repertoire sequencing (IR-seq) and flow cytometry were used to access vaccine-induced cellular immunity, which demonstrated that robust T cell responses (T cell activation, tissue-resident memory T cell (Trm) generation, and TCR clonal expansion) could be induced by intranasal vaccination. In summary, we identified the SARS-CoV-2-associated TCR repertoires profile, specific TCRs and T cell responses. This study provides a theoretical basis for developing effective immunization strategies | ||
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