Human major histocompatibility complex class I molecules presenting SARS-CoV-2-derived peptide epitopes (HLA-I/SARS-CoV-2 peptide complex)

Human major histocompatibility complex (MHC) class I molecules, also known as human leukocyte antigens (HLA), are essential components of the adaptive immune system that present intracellularly derived peptides to CD8+ cytotoxic T cells [1]. During a SARS-CoV-2 infection, viral proteins such as the Spike (S), Nucleocapsid (N), and Membrane (M) proteins are degraded by the host proteasome into short peptide fragments, typically 8 to 11 amino acids in length [2]. These peptides are then loaded onto HLA-I molecules in the endoplasmic reticulum and transported to the cell surface, where they serve as a signal of infection [3]. The recognition of these peptide-HLA complexes by specific T-cell receptors (TCRs) triggers the activation of T cells, leading to the destruction of the infected host cell and the secretion of pro-inflammatory cytokines [4]. In the context of drug development, these complexes are the primary targets for COVID-19 vaccines, which aim to induce the presentation of these epitopes to prime the immune system [5]. Furthermore, novel therapeutic approaches such as TCR-engineered T-cell (TCR-T) therapies and TCR-mimetic antibodies are being explored to specifically target and eliminate cells displaying these SARS-CoV-2-derived epitopes [6]. [1] https://www.uniprot.org/uniprotkb/P04439/entry [2] https://pubmed.ncbi.nlm.nih.gov/32544444/ [3] https://www.ncbi.nlm.nih.gov/books/NBK27156/ [4] https://pubmed.ncbi.nlm.nih.gov/33065005/ [5] https://www.nature.com/articles/s41577-020-00434-7 [6] https://pubmed.ncbi.nlm.nih.gov/34161771/

Other names

MHC-I/SARS-CoV-2 epitope complexHuman leukocyte antigen class I-SARS-CoV-2 peptide complexpMHC-I (SARS-CoV-2)HLA-I/peptide complex (COVID-19)

Presentation of intracellularly processed viral peptides to the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes to trigger the lysis of infected cells.