SARS-CoV-2 peptide–Human Leukocyte Antigen class I complex (SARS-CoV-2 pMHC-I) (SARS-CoV-2 pMHC-I)

SARS-CoV-2 peptide–Human Leukocyte Antigen (HLA) class I complexes are molecular structures formed on the surface of cells infected with the SARS-CoV-2 virus. These complexes consist of short viral protein fragments, typically 8-11 amino acids in length, bound within the peptide-binding groove of HLA class I molecules (Saini et al., Science Immunology, 2021). Their primary biological role is to serve as "red flags" for the immune system, allowing CD8+ cytotoxic T cells to identify and destroy infected host cells through T-cell receptor (TCR) recognition (Nguyen et al., Journal of Virology, 2021). In the context of COVID-19, these complexes are pivotal targets for advanced therapeutic strategies, including TCR-engineered T-cell (TCR-T) therapies and TCR-mimetic antibodies designed to provide precise viral clearance (He et al., Nature Communications, 2021). Because these complexes are specific to infected cells, they offer a way to target the virus intracellularly, which is not possible with standard neutralizing antibodies. However, the effectiveness of targeting these complexes is challenged by the high genetic diversity of HLA alleles across the human population and the potential for the virus to evolve mutations that escape T-cell detection (Nelde et al., Nature Communications, 2021). Therapeutic development often focuses on immunodominant peptides presented by common HLA alleles like HLA-A*02:01 to maximize population coverage. Safety concerns primarily involve the risk of off-target cross-reactivity with similar self-peptides found in healthy tissues, which could lead to autoimmunity.

Other names

SARS-CoV-2 peptide-MHC class I complexSARS-CoV-2 pMHC-IViral peptide-HLA complexSARS-CoV-2 antigen-HLA complexpMHC-I (SARS-CoV-2)

Targeted lysis of infected cells via TCR-mediated or TCR-mimetic recognition of viral peptide-HLA complexes, triggering granzyme and perforin release.