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

SARS-CoV-2 peptide–Human Leukocyte Antigen (HLA) class 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 are proteolytically degraded into short peptides (typically 8-11 amino acids) and loaded onto HLA class I molecules within the endoplasmic reticulum before being transported to the plasma membrane [1][2]. Their primary biological role is to serve as an 'identity card' for the immune system, allowing CD8+ cytotoxic T cells to recognize and eliminate infected cells through the binding of T-cell receptors (TCRs) to the peptide-HLA interface [2][3]. In therapeutic development, these complexes are targeted by TCR-engineered T cells and TCR-mimetic antibodies designed to provide precise, cell-mediated clearance of the virus, particularly in patients with impaired natural immunity [4]. However, the high polymorphism of HLA genes in the human population means that such therapies must be tailored to specific HLA alleles, such as HLA-A*02:01, and carefully screened to avoid off-target reactivity against healthy tissues [1][5]. Sources: [1] Huisman, W., et al. (2022). "The HLA-I-presented peptidome of SARS-CoV-2." Nature Communications. [2] Shomuradova, A. S., et al. (2020). "SARS-CoV-2 Epitopes Are Recognized by a Public and Diverse Repertoire of Human T Cell Receptors." Immunity. [3] Nguyen, A., et al. (2020). "Genetic Susceptibility to COVID-19: Analysis of HLA Class I Repertoire and ACE2 Polymorphisms." Journal of Virology. [4] Medigene AG. (2021). "TCR-T immunotherapies for the treatment of COVID-19." [5] Saini, S. K., et al. (2021). "SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8+ T cell activation in COVID-19 patients." Science Immunology.

Other names

SARS-CoV-2 pMHC-I complexSARS-CoV-2 peptide-MHC class I complexCOVID-19 peptide-HLA complexSARS-CoV-2 antigen-HLA complex

Binding of engineered T-cell receptors (TCRs) or TCR-like antibodies to the specific viral peptide-HLA complex, leading to the recruitment and activation of cytotoxic T cells to lyse the infected host cell.