SARS-CoV-2 spike protein-derived peptide-HLA complex (SARS-CoV-2 S-peptide-HLA)

The SARS-CoV-2 spike protein-derived peptide-HLA complex is a critical immunological target formed when host cells process the viral spike protein into short peptide fragments and present them on the cell surface via Human Leukocyte Antigen (HLA) Class I or Class II molecules (Grifoni et al., 2020, Cell). This complex serves as the essential ligand for T-cell receptors (TCRs), enabling the adaptive immune system to identify and respond to SARS-CoV-2 infection. HLA Class I complexes present peptides to CD8+ T cells, which directly kill infected cells, while HLA Class II complexes present to CD4+ T cells to orchestrate the overall immune response, including cytokine production and B-cell help (Saini et al., 2021, Science Immunology). Most COVID-19 vaccines, such as BNT162b2 and mRNA-1273, work by inducing host cells to synthesize the spike protein, which is then processed and presented as these peptide-HLA complexes to prime T-cell immunity (Sahin et al., 2020, Nature). These complexes are also the focus of diagnostic tools for monitoring cellular immunity and are being explored as targets for next-generation immunotherapies, including TCR-engineered T cells. The effectiveness of this target is influenced by the high polymorphism of HLA genes in the human population and the potential for viral variants to harbor mutations that disrupt peptide binding or TCR recognition (Dan et al., 2021, Science).

Other names

SARS-CoV-2 spike pMHC complexSpike protein HLA-presented epitopesSARS-CoV-2 S-peptide-MHCCOVID-19 spike T-cell epitopesSARS-CoV-2 spike peptide-MHC class I/II complex

Recognition of the peptide-HLA complex by specific T-cell receptors (TCRs) triggers the activation of CD8+ cytotoxic T cells or CD4+ helper T cells, leading to the elimination of infected cells and the production of antiviral cytokines.