{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:57Z","timestamp":1787026617782,"version":"build-2736575974"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the critical importance of understanding protective long-lasting immune responses. This study investigates the epitope specificity, T cell receptor (TCR) usage, and phenotypic changes in SARS-CoV-2-specfic CD8\n                      <jats:sup>+<\/jats:sup>\n                      and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells over time in convalescent individuals with COVID-19.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Peripheral blood mononuclear cells (PBMCs) were collected from 28 unvaccinated individuals with primary SARS-CoV-2 infection (6 identified as the D614G variant, clade 20C) and analyzed up to 12 months post-symptom onset. Antigen-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells were analyzed using flow cytometry and single-cell RNA sequencing (scRNAseq) using specific dextramer and antibody reagents. TCR clonotypes and activation markers were characterized to explore T cell dynamics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SARS-CoV-2-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells exhibited waning frequencies long-term, transitioning from memory-like to a na\u00efve-like state. scRNAseq revealed specificity against both spike and non-spike antigens with increased CD95 and CD127 expression over time, indicating that na\u00efve-like T cells may represent stem cell memory T cells, which are multipotent and self-renewing, likely important for long-lived immunity. TCR clonal expansion was observed mainly in memory T cells, with overlapping TCR beta chain (TRB)-complementary determining region 3 (CDR3) sequences between participants, suggesting shared public TCR epitope-specific repertoires against SARS-CoV-2. Further, unique spike-specific CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells with high CD95 and CD127 expression were identified, which may play a crucial role in long-term protection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study highlights epitope-specificity heterogeneity, with some immunodominant responses, and suggests a potential role for long-lived SARS-CoV-2-specific T cell immunity. Shared TCR repertoires offers insights into cross-reactive and protective T cell clones, providing valuable information for optimizing vaccine strategies against emerging SARS-CoV-2 variants. The findings underscore the critical role of cellular immunity in long-term protection against SARS-CoV-2 and emphasizes the importance of understanding T cell dynamics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1510436","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T02:30:23Z","timestamp":1740709823000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["T cell receptor usage and epitope specificity amongst CD8+ and CD4+ SARS-CoV-2-specific T cells"],"prefix":"10.3389","volume":"16","author":[{"given":"Ulrik","family":"Fahn\u00f8e","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander 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