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

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:17

Enthalten in:

Journal of hematology & oncology - 17(2024), 1 vom: 27. März, Seite 15

Sprache:

Englisch

Beteiligte Personen:

Zhang, Qian [VerfasserIn]
Liang, Qing [VerfasserIn]
Zhang, Rui [VerfasserIn]
Wang, Nan [VerfasserIn]
Xiao, Xu [VerfasserIn]
Shao, Jiahao [VerfasserIn]
Wang, Kejia [VerfasserIn]

Links:

Volltext

Themen:

Immune repertoire
Letter
Receptors, Antigen, T-Cell
Research Support, Non-U.S. Gov't
SARS-CoV-2
T cell immunity
T cell receptor
Vaccines

Anmerkungen:

Date Completed 29.03.2024

Date Revised 19.04.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1186/s13045-024-01537-6

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370288203