SARS-CoV-2 spike protein–derived peptides presented by HLA class I and II (SARS-CoV-2 Spike-HLA complex)

The SARS-CoV-2 spike protein–derived peptides presented by HLA class I and II are critical molecular complexes that mediate the cellular immune response to the virus. These complexes are formed when the viral spike protein is proteolytically processed into short peptides, which are then loaded onto Human Leukocyte Antigen (HLA) molecules for display on the cell surface (Grifoni et al., 2020, Cell). HLA class I complexes are recognized by CD8+ cytotoxic T cells, leading to the destruction of infected cells, while HLA class II complexes activate CD4+ helper T cells to coordinate the broader immune response, including B cell activation (Saini et al., 2021, Science Immunology). Most COVID-19 vaccines, such as mRNA and viral vector platforms, function by inducing the host's cells to produce these specific peptide-HLA complexes to prime T-cell memory (Sahin et al., 2020, Nature). Therapeutic development also explores the use of TCR-engineered T cells and TCR-like antibodies that specifically target these epitopes (Heitmann et al., 2022, Nature). A significant challenge in targeting these complexes is the high polymorphism of HLA genes in the human population and the potential for viral mutations to alter epitope presentation, leading to immune escape (Kared et al., 2021, JCI).

Other names

SARS-CoV-2 Spike epitopesSpike-HLA complexesSARS-CoV-2 Spike-derived MHC ligandsS-protein HLA-restricted peptides

Vaccines induce the expression of the spike protein, which is then processed into peptides and presented on HLA molecules to prime T-cell receptors (TCRs). Adoptive T-cell therapies use cells with TCRs specific for these peptide-HLA complexes to target and kill infected cells.