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| Home > Publications database > Promiscuous class II-binding SARS-CoV-2-nuc derived vaccine-peptide induced extensive conventional, innate and unconventional T cell responses. |
| Home > Publications database > Promiscuous class II-binding SARS-CoV-2-nuc derived vaccine-peptide induced extensive conventional, innate and unconventional T cell responses. |
| Journal Article | DKFZ-2025-02644 |
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2025
Frontiers Media
Lausanne
Abstract: 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.
Keyword(s): Humans (MeSH) ; SARS-CoV-2: immunology (MeSH) ; COVID-19: immunology (MeSH) ; COVID-19: prevention & control (MeSH) ; COVID-19 Vaccines: immunology (MeSH) ; Immunity, Innate (MeSH) ; T-Lymphocytes: immunology (MeSH) ; Receptors, Antigen, T-Cell, alpha-beta: immunology (MeSH) ; Nucleocapsid Proteins: immunology (MeSH) ; Adult (MeSH) ; HLA-DR Antigens: immunology (MeSH) ; Vaccines, Subunit: immunology (MeSH) ; CD1 restricted ; SARS-CoV-2 ; SARS-CoV-2 nucleoprotein peptide ; T cell response ; adaptive Vδ2γ9negative γδ T-cells ; peptide vaccine ; unconventional T cells ; vaccine peptide reactive Vδ1 γδ T-cells ; COVID-19 Vaccines ; Receptors, Antigen, T-Cell, alpha-beta ; Nucleocapsid Proteins ; HLA-DR Antigens ; Vaccines, Subunit
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