ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1676455
Promiscuous class II-binding SARS-CoV-2-nuc derived vaccine-peptide induced extensive conventional, innate and unconventional T cell responses
Provisionally accepted
- 1University of Tübingen, Tübingen, Germany
- 2Childrens Hospital University Tübingen, Tübingen, Germany
- 3Institut of Immunology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany, Tübingen, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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 TCRα, -β, -γ and -δ chains in T cells responding ex-vivo to the vaccine peptide LLLLDRLLNQLESKMS with IFNγ+-secretion. Adaptive repertoires were unique. Donors shared 15 TCRα and 9 TCRβ clonotypes, all public, showing no conserved motifs but TdT-independent "neonatal" CDR3 regions close to the germline. Half the wtSARS-CoV-2 nucleocapsid-reactive adaptive clonotypes show preferential V-segment usage (6/64 Vα and 4-8/45 Vβ chains), and all share/show a N-nucleotide-encoded hydrophobicity in their CDR3 region. VδCα rearrangements (20.4% and 15.3% of the TCRα-repertoires, respectively), Vδ1Cδ γδ-clonotypes homologous to public CD1-restricted Vδ1+ γδTCRs, and the induction of "adaptive" Vδ2Vγ9negative T cells support the role of innate T cells in the immune response. Words 150
Keywords: SARS-CoV-2, Peptide vaccine, nuc peptide, T cell response, Unconventional T cells
Received: 30 Jul 2025; Accepted: 07 Oct 2025.
Copyright: © 2025 Schilbach, Krickeberg and Rammensee. 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: Karin Schilbach, karin.schilbach@med.uni-tuebingen.de
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.