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

The SARS-CoV-2 membrane protein (M protein) is the most abundant structural protein of the virus and plays a central role in viral assembly and morphogenesis (UniProt P0DTC5). During the viral life cycle, M protein-derived peptides are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I and Class II molecules (PubMed: 32473127). These peptide-MHC (pMHC) complexes serve as critical recognition elements for the adaptive immune system, specifically for CD8+ and CD4+ T cells (PubMed: 32730210). Recognition of these complexes by T-cell receptors (TCRs) triggers the destruction of infected cells and the release of antiviral cytokines. Because the M protein is highly conserved across SARS-CoV-2 variants, these pMHC complexes are attractive targets for the development of variant-proof vaccines and TCR-based immunotherapies. Therapeutic strategies, such as multi-antigen vaccines (e.g., GRT-R910) or TCR-engineered T cells, aim to provide broader and more durable protection than those targeting the Spike protein alone. However, the effectiveness of these therapies is often limited by the specific HLA alleles of the patient, necessitating a personalized or multi-allele approach.

Other names

SARS-CoV-2 M protein epitopesSARS-CoV-2 membrane protein HLA-restricted peptidesM-derived pMHCSARS-CoV-2 M protein-derived peptides presented by MHC molecules

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on CD8+ or CD4+ T cells, leading to the lysis of infected cells and the secretion of pro-inflammatory cytokines.