SARS-CoV-2 membrane protein-derived peptides presented on human leukocyte antigen (SARS-CoV-2 M-peptide-HLA complex)

The SARS-CoV-2 membrane (M) protein is the most abundant structural protein of the virus and is essential for viral assembly and morphogenesis. Peptides derived from the M protein are naturally processed by host cells and presented on the cell surface via human leukocyte antigen (HLA) class I and class II molecules. These peptide-HLA (pMHC) complexes are critical targets for the adaptive immune system, specifically recognized by T-cell receptors (TCRs) on cytotoxic CD8+ and helper CD4+ T cells. Recognition of these complexes triggers a robust immune response, including the secretion of pro-inflammatory cytokines like interferon-gamma and the direct destruction of infected cells. Because the M protein is highly conserved across different SARS-CoV-2 variants compared to the spike protein, these M-derived pMHC complexes are considered high-value targets for next-generation vaccines and adoptive T-cell therapies. Such therapeutic approaches aim to provide broader and more durable protection against COVID-19, especially for patients who do not respond well to antibody-based vaccines. However, the high polymorphism of HLA alleles and the risk of off-target cross-reactivity with self-antigens remain significant challenges in the development of these therapies.

Other names

SARS-CoV-2 M protein epitopesHLA-restricted SARS-CoV-2 M peptidesM-peptide/MHC complexSARS-CoV-2 membrane protein immunopeptidomeSARS-CoV-2 M-derived pMHC

T-cell receptor (TCR) mediated recognition of the peptide-HLA complex leading to T-cell activation, cytokine release, and lysis of infected cells.