SARS-CoV-2 nucleocapsid protein-derived peptides presented by HLA class I and II (SARS-CoV-2 N-peptide-HLA complex)

The SARS-CoV-2 nucleocapsid (N) protein-derived peptides presented by HLA class I and II molecules are essential targets for the host's adaptive immune system during COVID-19 infection. The N protein is a highly conserved and abundantly expressed structural protein that encapsulates the viral RNA genome (UniProt P0DTC9). During infection, the N protein is proteolytically processed into short peptides that are loaded onto Human Leukocyte Antigen (HLA) molecules. HLA Class I molecules present these peptides to CD8+ cytotoxic T cells, which directly kill infected cells, while HLA Class II molecules present them to CD4+ helper T cells to orchestrate B-cell and T-cell memory (Grifoni et al., 2020, Cell). Because the N protein accumulates fewer mutations than the Spike protein, these peptide-HLA complexes are considered high-value targets for variant-proof vaccines and adoptive T-cell therapies (Le Bert et al., 2020, Nature). Therapeutic strategies targeting this complex aim to induce robust cellular immunity that can recognize and eliminate cells harboring the virus, regardless of surface protein mutations.

Other names

SARS-CoV-2 N protein epitopesNucleocapsid-derived HLA ligandsSARS-CoV-2 N-MHC complexSARS-CoV-2 nucleoprotein epitopesN-derived T-cell epitopes

Recognition by T-cell receptors (TCRs) on CD4+ and CD8+ T cells to trigger an adaptive immune response against virally infected cells.