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

SARS-CoV-2 peptide–Major Histocompatibility Complex class I (pMHC-I) 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 or Nucleocapsid proteins, are degraded by the host proteasome into short peptides, which are then loaded onto MHC class I molecules in the endoplasmic reticulum and transported to the plasma membrane (Nguyen et al., 2021, Nature). The primary biological function of these complexes is to present viral antigens to CD8+ cytotoxic T lymphocytes, which recognize the specific peptide-MHC combination via their T-cell receptors (TCRs) to initiate an antiviral response. In the context of COVID-19, these complexes serve as critical targets for the development of next-generation immunotherapies, including TCR-mimetic antibodies and TCR-engineered T cells, which aim to selectively eliminate infected cells (He et al., 2021, Nature Communications). Because these complexes are only present on cells containing viral proteins, they offer a high degree of specificity compared to traditional antiviral drugs. However, the high diversity of human leukocyte antigen (HLA) alleles and the potential for viral mutations to alter the presented peptides remain significant challenges for broad therapeutic application (Sette & Crotty, 2021, Cell).

Other names

SARS-CoV-2 peptide-HLA class I complexCOVID-19 pMHC-ISARS-CoV-2 antigen-MHC complexpMHC-I (SARS-CoV-2)

Therapeutic agents such as TCR-mimetic antibodies or engineered T-cells bind specifically to the viral peptide nestled within the MHC-I groove on the surface of infected cells. This binding triggers immune-mediated destruction of the infected cell via perforin/granzyme release or antibody-dependent cellular cytotoxicity (ADCC), thereby limiting viral replication and spread (He et al., 2021, Nature Communications; Sette & Crotty, 2021, Cell).