NGS-based bulk TCR-repertoire analysis of peptide-specific T-cell responses 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
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 TCRa, -ß, -? and -d chains in T cells responding ex-vivo to the vaccine peptide LLLLDRLLNQLESKMS with IFN?+-secretion. Adaptive repertoires were unique. Donors shared 15 TCRa and 9 TCRß 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 Va and 4-8/45 Vß chains), and all share/show a N-nucleotide-encoded hydrophobicity in their CDR3 region. VdCa rearrangements (20.4% and 15.3% of the TCRa-repertoires, respectively), Vd1Cd ?d-clonotypes homologous to public CD1-restricted Vd1+ ?dTCRs, and the induction of "adaptive" Vd2V?9negative T cells support the role of innate T cells in the immune response.