SARS-CoV-2 nucleocapsid protein–derived peptide epitopes presented on HLA class I (SARS-CoV-2 N-HLA-I)

The SARS-CoV-2 nucleocapsid (N) protein is a highly abundant and conserved structural protein responsible for packaging the viral RNA genome into a helical ribonucleoprotein complex (UniProt P0DTC9). During the viral life cycle, the N protein is proteolytically processed into short peptide fragments, which are subsequently presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules (PubMed: 32591409). These peptide-HLA complexes serve as critical signals for the adaptive immune system, specifically allowing CD8+ cytotoxic T cells to identify and eliminate infected cells. Because the N protein is less prone to mutations compared to the Spike protein, these epitopes are considered high-priority targets for developing variant-proof vaccines and T-cell therapies (PubMed: 33065045). Therapeutic interventions, such as TCR-engineered T cells or multi-epitope peptide vaccines like CoVac-1, aim to leverage these complexes to provide durable and broad protection against COVID-19 (NCT04545606).

Other names

SARS-CoV-2 N protein epitopesNucleocapsid peptide-MHC class I complexSARS-CoV-2 N-HLA-I complexSARS-CoV-2 N-derived pMHC

T-cell receptor (TCR) mediated recognition of the peptide-HLA complex leads to the activation of CD8+ cytotoxic T lymphocytes, which subsequently induce apoptosis in the target cell via the release of perforins and granzymes (PubMed: 32591409).