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

SARS-CoV-2 peptide–Major Histocompatibility Complex (pMHC) complexes are molecular assemblies displayed on the surface of host cells following infection by the SARS-CoV-2 virus. These complexes are formed when viral proteins, such as the Spike, Nucleocapsid, or Membrane proteins, are processed by the host proteasome into short peptides (typically 8-11 amino acids for MHC Class I) and loaded onto MHC molecules within the endoplasmic reticulum (Shomuradova et al., 2020, Immunity). The primary biological role of these complexes is to serve as a signal for the adaptive immune system, specifically allowing CD8+ cytotoxic T-cells to identify and destroy infected cells via T-cell receptor (TCR) recognition (Huisman et al., 2022, Frontiers in Immunology). In therapeutic development, SARS-CoV-2 pMHC complexes are targeted by novel modalities such as TCR-mimetic antibodies and TCR-engineered T-cells, which aim to eliminate the cellular reservoirs of the virus that are inaccessible to standard neutralizing antibodies (Nguyen et al., 2021, Nature Communications). While highly specific to the infected state, the clinical utility of targeting these complexes is constrained by the high polymorphism of Human Leukocyte Antigen (HLA) genes, requiring therapies to be tailored to specific HLA alleles like HLA-A*02:01. Furthermore, the potential for viral mutations to alter peptide sequences poses a risk of immune escape, necessitating the targeting of highly conserved viral epitopes.

Other names

SARS-CoV-2 pMHCSARS-CoV-2 peptide-HLA complexHLA-presented SARS-CoV-2 epitopesSARS-CoV-2 antigen-MHC complex

Targeting of infected cells for immune-mediated lysis by mimicking T-cell receptor recognition of viral epitopes presented on MHC molecules.