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Immunol."],"abstract":"<jats:p>\n                    We describe the T-cell response of two healthy SARS-CoV-2-unexposed volunteers to a SARS-CoV-2 nucleoprotein-derived vaccine peptide predicted to promiscuously bind multiple HLA-DR allotypes. NGS-based bulk TCR-repertoire analysis of peptide-specific T-cell responses 4 (D2) and 27 (D1) weeks after vaccination identified CDR3 regions of TCR\u03b1, -\u03b2, -\u03b3 and -\u03b4 chains in T cells responding\n                    <jats:italic>ex-vivo<\/jats:italic>\n                    to the vaccine peptide LLLLDRLNQLESKMS with IFN\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    -secretion. Adaptive repertoires were unique. Donors shared 15 TCR\u03b1 and 9 TCR\u03b2 clonotypes, all public, showing no conserved motifs but TdT-independent \u201cneonatal\u201d CDR3 regions close to the germline. Half the wtSARS-CoV-2 nucleocapsid-reactive adaptive clonotypes show preferential V-segment usage (6\/64 V\u03b1 and 4-8\/45 V\u03b2 chains), and all share\/show a N-nucleotide-encoded hydrophobicity in their CDR3 region. V\u03b4C\u03b1 rearrangements (20.4% and 15.3% of the TCR\u03b1-repertoires, respectively), V\u03b41C\u03b4 \u03b3\u03b4-clonotypes homologous to public CD1-restricted V\u03b41\n                    <jats:sup>+<\/jats:sup>\n                    \u03b3\u03b4TCRs, and the induction of \u201cadaptive\u201d V\u03b42V\u03b39\n                    <jats:sup>negative<\/jats:sup>\n                    T cells support the role of innate T cells in the immune response.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1676455","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T06:32:03Z","timestamp":1762842723000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Promiscuous class II-binding SARS-CoV-2-nuc derived vaccine-peptide induced extensive conventional, innate and unconventional T cell responses"],"prefix":"10.3389","volume":"16","author":[{"given":"Naomi","family":"Krickeberg","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Children\u2019s Hospital T\u00fcbingen","place":["T\u00fcbingen, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Georg","family":"Rammensee","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University of T\u00fcbingen","place":["T\u00fcbingen, Germany"]},{"name":"German Cancer Consortium (DKTK), partner site T\u00fcbingen, a partnership between DKFZ and University Hospital T\u00fcbingen, Germany, Cluster of Excellence iFIT (EXC2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen","place":["T\u00fcbingen, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Schilbach","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Children\u2019s Hospital T\u00fcbingen","place":["T\u00fcbingen, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2006392117","article-title":"Demographic perspectives on the mortality of COVID-19 and other epidemics","volume":"117","author":"Goldstein","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2020.7968","article-title":"Risk Factors Associated With All-Cause 30-Day Mortality in Nursing Home Residents With COVID-19","volume":"181","author":"Panagiotou","year":"2021","journal-title":"JAMA Intern Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp2009575","article-title":"Severe Covid-19","volume":"383","author":"Berlin","year":"2020","journal-title":"N Engl J 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