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

SARS-CoV-2 peptide-Major Histocompatibility Complex (pMHC) represents the molecular assembly of viral protein fragments—derived from the spike, membrane, or nucleocapsid proteins—bound to Human Leukocyte Antigen (HLA) molecules on the surface of infected cells. This complex is the fundamental unit recognized by the T-cell receptor (TCR) of CD8+ T-cells, initiating a targeted immune response to destroy the infected cell (Nguyen et al., 2021, PMID: 33051876). While most COVID-19 therapeutics focus on the spike protein, pMHC complexes involving the more conserved membrane and nucleocapsid proteins offer opportunities for broader, variant-resistant immunity (Saini et al., 2021, PMID: 33544075). These complexes are being actively explored as targets for TCR-engineered T-cell therapies and TCR-like monoclonal antibodies, which aim to mimic the specificity of the immune system to treat severe or persistent infections (Huisman et al., 2022, PMID: 35710800). Challenges in targeting these complexes include the high degree of HLA polymorphism in the human population and the risk of cross-reactivity with self-peptides, which could lead to autoimmune adverse effects.

Other names

SARS-CoV-2 pMHC complexHLA-presented SARS-CoV-2 epitopesSpike/Membrane/Nucleocapsid-MHC complexesSARS-CoV-2 antigen-MHC complexHLA-A*02:01 SARS-CoV-2 peptide complex

Recognition of the pMHC complex by CD8+ T-cell receptors (TCRs) or engineered TCR-like agents triggers the activation of cytotoxic T-lymphocytes, leading to the release of cytotoxic granules (perforin/granzyme) and the subsequent apoptosis of the infected host cell.