Non-structure protein ORF1ab (NSP8) in SARS-CoV-2 contains potential gamma delta T cell epitopes

Upon activation by the pathogen through T-cell receptors (TCRs), gamma delta T cells suppress the pathogenic replication and thus play important roles against viral infections. Targeting SARS-CoV-2 via gamma delta T cells provides alternative therapeutic strategies. However, little is known about the recognition of SARS-CoV-2 antigens by gamma delta T cells. We discovered a specific V gamma 9/delta 2 CDR3 by analyzing gamma delta T cells derived from the patients infected by SARS-CoV-2. Using a cell model exogenously expressing gamma delta-TCR established, we further screened the structural motifs within the CDR3 responsible for binding to gamma delta-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 gamma delta T cells and thus could serve as a potential target for vaccines.