Severe acute respiratory syndrome coronavirus 2 spike protein-derived peptide–human leukocyte antigen complex (SARS-CoV-2 spike peptide–HLA complex)

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-derived peptide–human leukocyte antigen (HLA) complex is a critical immunological assembly that mediates the cellular immune response against COVID-19. These complexes consist of short, proteolytically processed fragments of the viral spike protein (epitopes) bound within the groove of HLA Class I or Class II molecules on the surface of infected or antigen-presenting cells (Grifoni et al., 2020, Cell). Recognition of these pMHC (peptide-MHC) complexes by the T-cell receptors (TCRs) of CD8+ and CD4+ T-cells is the primary mechanism for identifying and eliminating virally infected host cells (Saini et al., 2021, Sci Immunol). In drug development, these complexes are the functional targets of most COVID-19 vaccines, which work by inducing the expression of spike protein to generate these complexes and prime T-cell memory (Sahin et al., 2020, Nature). Furthermore, they are being targeted by novel therapeutic modalities such as TCR-engineered T-cell therapies and soluble TCR-bispecifics, which aim to provide passive cellular immunity or enhance the endogenous response. A significant challenge in targeting these complexes is the high degree of HLA polymorphism in the human population, which necessitates the identification of promiscuous epitopes or the development of personalized approaches (Harvey et al., 2021, Nat Rev Microbiol).

Other names

SARS-CoV-2 S-peptide–MHC complexSpike-derived epitope–HLA complexpMHC complexSARS-CoV-2 spike antigen–HLA complex

T-cell receptor-mediated recognition of viral epitopes presented by HLA molecules, leading to cytotoxic T-lymphocyte activation, cytokine production, and elimination of infected cells.