SARS-CoV-2 Peptide-Major Histocompatibility Complex (SARS-CoV-2 pMHC)

SARS-CoV-2 peptide-Major Histocompatibility Complex (pMHC) refers to the molecular assembly of viral epitopes—derived from proteins such as Spike (S), Nucleocapsid (N), and Membrane (M)—bound within the groove of MHC class I or class II molecules (HLA in humans) [2, 8, 15]. These complexes are presented on the surface of infected cells or professional antigen-presenting cells, serving as the primary signal for T-cell recognition via the T-cell receptor (TCR) [8, 11, 20]. This interaction is critical for the induction of adaptive immunity, where MHC-I complexes activate CD8+ cytotoxic T cells to kill infected cells, and MHC-II complexes activate CD4+ helper T cells to coordinate the broader immune response [7, 15, 22]. In therapeutic development, these pMHC complexes are targeted by TCR-engineered T cells (TCR-T), soluble TCR-based biologics, and multi-peptide vaccines like CoVac-1 to provide durable protection against COVID-19 [8, 9, 17, 19]. However, the high polymorphism of HLA alleles and the rapid evolution of SARS-CoV-2 variants pose significant challenges, as mutations can disrupt pMHC formation or TCR binding, leading to immune evasion [4, 14, 18, 22]. Furthermore, the potential for cross-reactivity with self-antigens necessitates rigorous safety screening to avoid autoimmune-like toxicities [2, 12].

Other names

SARS-CoV-2 pMHCSARS-CoV-2 peptide-HLA complexHLA-presented SARS-CoV-2 epitopesSARS-CoV-2 antigen-MHC complexSARS-CoV-2 peptide-Major Histocompatibility Complex

The target complex is recognized by the T-cell receptor (TCR) of CD8+ or CD4+ T cells, which triggers a signaling cascade leading to T-cell activation, proliferation, and the release of cytotoxic granules or cytokines to eliminate infected cells [8, 11, 20, 22].