SARS-CoV-2 membrane protein peptide-MHC complex (SARS-CoV-2 M-pMHC)

The SARS-CoV-2 membrane (M) protein is the most abundant structural protein of the virus and plays a critical role in viral assembly and morphogenesis. During infection, the M protein is synthesized within the host cell, and fragments, particularly from the C-terminal endodomain, are processed by the proteasome and loaded onto Major Histocompatibility Complex (MHC) class I molecules for presentation on the cell surface. These peptide-MHC (pMHC) complexes serve as highly specific signatures of infection, allowing the cellular immune system to distinguish infected cells from healthy ones. Because the M protein is highly conserved across SARS-CoV-2 variants, these pMHC complexes are attractive targets for next-generation immunotherapies, such as TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers. These therapeutic approaches aim to bypass natural immune exhaustion by providing high-affinity recognition of the M-peptide-MHC complex, leading to the direct elimination of the viral reservoir in the host. Research has identified specific immunodominant epitopes within the C-terminal region that are frequently presented by common HLA alleles like HLA-A*02:01, making them viable candidates for broad clinical application.

Other names

SARS-CoV-2 M protein-derived peptide-HLA complexM-peptide-MHC class I complexSARS-CoV-2 membrane protein antigen-presenting complexpMHC (SARS-CoV-2 M protein)

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or bispecific molecules triggers T-cell mediated lysis of infected host cells and the release of pro-inflammatory cytokines to clear the viral infection.