biostudies-literatureUnknown13Du BHealth Commission of Hubei ProvinceNatural Science Foundation of Hubei ProvinceUpon activation by the pathogen through T-cell receptors (TCRs), γδT cells suppress the pathogenic replication and thus play important roles against viral infections. Targeting SARS-CoV-2 <i>via</i> γδT cells provides alternative therapeutic strategies. However, little is known about the recognition of SARS-CoV-2 antigens by γδT cells. We discovered a specific Vγ9/δ2 CDR3 by analyzing γδT cells derived from the patients infected by SARS-CoV-2. Using a cell model exogenously expressing γδ-TCR established, we further screened the structural motifs within the CDR3 responsible for binding to γδ-TCR. Importantly, these sequences were mapped to NSP8, a non-structural protein in SARS-CoV-2. Our results suggest that NSP8 mediates the recognition by γδT cells and thus could serve as a potential tarFrontiers in microbiology936272https://www.ebi.ac.uk/biostudies/studies/S-EPMC9354780biostudies-literatureNon-structure protein ORF1ab (NSP8) in SARS-CoV-2 contains potential γδT cell epitopes.PMC9354780Li GXi XDu BGuo YZhu YWang YfalseNon-structure protein ORF1ab (NSP8) in SARS-CoV-2 contains potential γδT cell epitopes.Upon activation by the pathogen through T-cell receptors (TCRs), γδT cells suppress the pathogenic replication and thus play important roles against viral infections. Targeting SARS-CoV-2 <i>via</i> γδT cells provides alternative therapeutic strategies. However, little is known about the recognition of SARS-CoV-2 antigens by γδT cells. We discovered a specific Vγ9/δ2 CDR3 by analyzing γδT cells derived from the patients infected by SARS-CoV-2. Using a cell model exogenously expressing γδ-TCR established, we further screened the structural motifs within the CDR3 responsible for binding to γδ-TCR. Importantly, these sequences were mapped to NSP8, a non-structural protein in SARS-CoV-2. Our results suggest that NSP8 mediates the recognition by γδT cells and thus could serve as a potential tar2022-01-01T00:00:00Z20222025-04-26T13:07:40.435Z2025-04-06T14:07:23.547ZS-EPMC93547803593523610.3389/fmicb.2022.936272