{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:36:47Z","timestamp":1764139007005,"version":"3.46.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006489","name":"Commissariat \u00e0 l'\u00c9nergie Atomique et aux \u00c9nergies Alternatives","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006489","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00c9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"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>This study provides an in-depth analysis of the diversity of the CD4 TCR CDR3\u03b2 repertoire specific to influenza A (HA) and Epstein-Barr virus (EBNA) epitopes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Epitope-specific CD4 T cells from 13 healthy donors were enriched using a short-term culture step, isolated based on activation markers, and sequenced for their TCR CDR3\u03b2 region using high-throughput sequencing. The frequency of each clonotype was then identified within the complete circulating CD4 T-cell CDR3\u03b2 repertoire.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>For both epitopes, the clonotype distribution was markedly skewed, with a small number of highly expanded clones comprising approximately 60% of the repertoire, alongside numerous low-frequency clonotypes. VJ gene usage and motif preferences differed between the two peptides, highlighting epitope-specific TCR selectivity. The response was predominantly composed of private T-cell clonotypes. The proportion of public clonotypes can increase among donors sharing HLA class II molecules and reveals in HLA-unrelated donors the level of TCR promiscuity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Overall, our data demonstrate that CD4 T-cell responses to these viral epitopes are polyclonal and highly personalized. The modest overlap of clonotypes between donors, coupled with a long tail of low-frequency clones, suggests that the full diversity of the epitope-specific T-cell repertoire is likely broader than previously estimated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1713225","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:33:57Z","timestamp":1764138837000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Deep exploration of the TCR CDR3\u03b2 repertoire specific for viral CD4 T-cell epitopes inside the circulating T-cell 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