SARS-CoV-2 membrane protein-derived peptide–HLA complexes (SARS-CoV-2 M-pMHC)

The SARS-CoV-2 membrane (M) protein is the most abundant structural protein of the virus, playing a pivotal role in virion assembly, morphogenesis, and the regulation of host immune responses. Peptides derived from the M protein are processed by the host cell and presented on the cell surface in complex with Human Leukocyte Antigen (HLA) molecules, forming peptide-HLA (pMHC) complexes. These complexes serve as the primary targets for T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes and CD4+ helper T cells, which are essential for viral clearance and the establishment of long-term immunity. Because the M protein is highly conserved across SARS-CoV-2 variants, its pMHC complexes are considered high-priority targets for next-generation universal vaccines and adoptive T-cell therapies. Therapeutic strategies, such as multi-antigen mRNA vaccines and TCR-engineered T-cell therapies, aim to elicit robust cellular immunity that remains effective even against variants that evade Spike-specific neutralizing antibodies. However, the high polymorphism of HLA molecules necessitates the identification of immunodominant epitopes restricted to common alleles to ensure broad population coverage.

Other names

SARS-CoV-2 M protein-derived peptide-MHC complexesSARS-CoV-2 membrane protein epitopesM-HLA complexesSARS-CoV-2 M-pMHCSARS-CoV-2 membrane protein-derived pMHC

T-cell receptor (TCR) mediated recognition of viral peptides presented by HLA molecules, leading to the activation of cytotoxic CD8+ T cells and helper CD4+ T cells for the elimination of infected cells.