Peptide–MHC complexes presenting SARS-CoV-2 antigens (SARS-CoV-2 pMHC)

Peptide–MHC (pMHC) complexes presenting SARS-CoV-2 antigens are the primary molecular targets for T-cell-mediated immunity during COVID-19 infection. These complexes are formed when viral proteins, such as the Spike, Nucleocapsid, or Membrane proteins, are processed into short peptides and displayed on the cell surface by Major Histocompatibility Complex (MHC) molecules. Recognition of these pMHC complexes by T-cell receptors (TCRs) triggers the activation of CD8+ cytotoxic T cells and CD4+ helper T cells, which are crucial for eliminating infected cells and coordinating the overall immune response. SARS-CoV-2 employs several strategies to evade this detection, including the downregulation of MHC molecules and the accumulation of mutations in key epitopes that disrupt TCR binding. Consequently, these complexes have become a focal point for the development of next-generation therapeutics, such as TCR-engineered T cells (TCR-T) and TCR-like antibodies, which can specifically target conserved viral fragments. These therapies aim to provide potent, long-lasting protection that is less susceptible to the viral mutations that often render neutralizing antibodies ineffective. Clinical efforts also include the use of off-the-shelf virus-specific T cells (VSTs) and multi-epitope peptide vaccines designed to enhance the presentation and recognition of these critical immune targets.

Other names

SARS-CoV-2 peptide-HLA complexesSARS-CoV-2 pHLA complexesSARS-CoV-2 epitope-MHC complexesSARS-CoV-2 pMHCSARS-CoV-2 antigen-presenting complexes

Recognition by T-cell receptors (TCRs) or TCR-like molecules to trigger cytotoxic killing of infected cells or immune activation through cytokine release.