SARS-CoV-2 peptide–Major Histocompatibility Complex (MHC) class I and II complexes (SARS-CoV-2 pMHC)

SARS-CoV-2 peptide–Major Histocompatibility Complex (MHC) class I and II complexes are molecular assemblies found on the surface of cells infected with the SARS-CoV-2 virus. These complexes consist of short viral protein fragments, known as epitopes, bound within the groove of MHC molecules, which are also referred to as Human Leukocyte Antigens (HLA) in humans (Huisman et al., 2022, Frontiers in Immunology). MHC class I complexes typically present peptides derived from internal viral proteins, such as the Nucleocapsid or Spike protein, to CD8+ cytotoxic T cells, signaling the immune system to destroy the infected cell. MHC class II complexes are primarily found on professional antigen-presenting cells and present peptides to CD4+ helper T cells to coordinate the broader adaptive immune response, including B-cell activation and cytokine production (Saini et al., 2021, Science Immunology). These complexes are the fundamental targets for T-cell-mediated immunity and are increasingly being explored for therapeutic interventions, particularly for patients who do not respond well to traditional vaccines. Novel therapies include T-cell receptor (TCR)-engineered T cells and TCR-like monoclonal antibodies, which are designed to provide highly specific recognition of these viral pMHC complexes (He et al., 2021, Nature Communications). Unlike traditional antibodies that target the surface of the virus, these therapies can target internal viral proteins that are often more conserved across different variants. However, the high diversity of HLA alleles in the human population and the potential for cross-reactivity with self-peptides present significant therapeutic challenges and safety concerns (Nagler et al., 2021, Journal of Clinical Investigation).

Other names

SARS-CoV-2 peptide-HLA complexesSARS-CoV-2 pMHCSARS-CoV-2 antigen-MHC complexesSARS-CoV-2 epitope-HLA complexes

Recognition of specific viral peptide-MHC complexes by T-cell receptors (TCRs) or TCR-like molecules to induce targeted lysis of infected cells or cytokine production (He et al., 2021, Nature Communications).