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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1510436

T Cell Receptor usage and epitope specificity amongst CD8 + and CD4 + SARS-CoV-2-specific T cells

Provisionally accepted
Ulrik Fahnøe Ulrik Fahnøe 1Shan Feng Shan Feng 1Alexander Underwood Alexander Underwood 1Kivin Jacobsen Kivin Jacobsen 2Amir Ameri Amir Ameri 2Thomas H. Blicher Thomas H. Blicher 2Christina S. Sølund Christina S. Sølund 3Brad Rosenberg Brad Rosenberg 4Nina Weis Nina Weis 3Liselotte Brix Liselotte Brix 2Jens Bukh Jens Bukh 1*
  • 1 University of Copenhagen, Copenhagen, Denmark
  • 2 Immudex, Virum, Denmark
  • 3 Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
  • 4 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States

The final, formatted version of the article will be published soon.

    As T cells are involved with protection against coronavirus disease 2019 (COVID-19), understanding their dynamics is vital for defining long-term outcomes. Peripheral blood mononuclear cells (PBMCs) from 28 unvaccinated individuals with primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (6 identified as the D614G variant, clade 20C) were analyzed up to 12 months (12M) post-symptom onset for antigen-specific T cells. Additionally, four of the 28 subjects were selected for single-cell RNA sequencing (scRNAseq) to evaluate in greater detail the T cell responses. SARS-CoV-2-specific CD8+ T cells waned overtime, suggesting protection may be of limited duration. These T cells shifted from transient memory-like to a naïve-like phenotype. scRNAseq revealed specificity against spike and non-spike antigens with increased CD95 and CD127 expression overtime, indicating that naïve-like T cells may be stem cell memory T cells, which are multipotent self-renewing T cells, likely important for long-lived immunity. T cell receptor (TCR) clonal expansion occurred mainly in memory T cells, with overlap of TCR beta chain (TRB)-complementary determining region 3 (CDR3) sequence between participants, suggesting public TCR epitope-specific repertoires against SARS-CoV-2. Further, unique spike-specific CD4+ T cells with high CD95 and CD127 expression were identified, which may be important for long-term protection. This study highlights epitope-specificity heterogeneity, with some immunodominant responses, and underscores a potential role for long-lived SARS-CoV-2-specific immunity through T cells. These findings provide insights into SARS-CoV-2-specific T cell dynamics of importance for optimizing future vaccine strategies.

    Keywords: SARS-CoV-2, COVID-19, T cells, Flow Cytometry, single-cell RNA sequencing, Transcriptomics, CD4 + -specific cells, CD8 + -specific cells

    Received: 12 Oct 2024; Accepted: 02 Jan 2025.

    Copyright: © 2025 Fahnøe, Feng, Underwood, Jacobsen, Ameri, Blicher, Sølund, Rosenberg, Weis, Brix and Bukh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jens Bukh, University of Copenhagen, Copenhagen, Denmark

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