SARS-CoV-2 spike protein–derived peptide epitopes presented on HLA class I (SARS-CoV-2 S-peptide/HLA-I)

The SARS-CoV-2 spike protein–derived peptide epitopes presented on HLA class I represent a critical interface between the virus and the host's adaptive immune system (Grifoni et al., 2020, Cell). During infection or after vaccination, the viral spike protein is processed into short peptides within the host cell and loaded onto Human Leukocyte Antigen (HLA) class I molecules for presentation on the cell surface (Sahin et al., 2020, Nature). These peptide-MHC (pMHC) complexes are specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which then trigger the apoptosis of the presenting cell to limit viral replication (Shomuradova et al., 2020, Immunity). This target is central to the efficacy of COVID-19 vaccines and is a focus for developing next-generation immunotherapies, such as TCR-engineered T cells and peptide-MHC-specific antibodies (Saini et al., 2021, Science Immunology). Because HLA molecules are highly polymorphic, the specific epitopes presented vary significantly across the human population, influencing individual immune responses and disease outcomes. Therapeutic strategies targeting these complexes must account for both the high mutational rate of the SARS-CoV-2 virus and the diversity of the human HLA repertoire.

Other names

SARS-CoV-2 spike peptide-MHC class I complexSpike-derived HLA-I epitopespMHC-I (SARS-CoV-2 Spike)SARS-CoV-2 S-epitope/HLA-I complex

Recognition by CD8+ T-cell receptors (TCRs) on cytotoxic T lymphocytes, leading to the release of perforins and granzymes and subsequent apoptosis of the infected or presenting cell (Shomuradova et al., 2020, Immunity).