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) refers to the molecular assembly of short viral peptide fragments (epitopes) bound to human leukocyte antigen (HLA) class I molecules on the surface of infected cells (Grifoni et al., 2020, Cell). These epitopes, typically 8 to 11 amino acids in length, are derived from the proteasomal degradation of SARS-CoV-2 proteins such as Spike (S), Nucleocapsid (N), and various non-structural proteins (Sette & Crotty, 2021, Cell). The primary biological function of this complex is to present intracellular viral antigens to the adaptive immune system, specifically serving as the ligand for the T-cell receptor (TCR) on CD8+ cytotoxic T lymphocytes (CTLs) (Le Bert et al., 2020, Nature). Upon recognition of the pMHC-I complex, CTLs are activated to eliminate the infected cell through the secretion of cytotoxic granules containing perforin and granzymes, thereby limiting viral spread. In clinical practice, these complexes are the fundamental targets of COVID-19 vaccines, which aim to prime the immune system to recognize these epitopes upon natural infection (Sahin et al., 2020, Nature). They are also the focus of emerging therapeutic strategies, including adoptive T-cell transfer and TCR-engineered T-cell (TCR-T) therapies, which seek to enhance the cellular immune response in immunocompromised or severely ill patients (Panagioti et al., 2021, Frontiers in Immunology). However, the effectiveness of targeting these complexes is influenced by HLA polymorphism across human populations and the potential for viral mutations to alter epitope sequences, leading to immune escape (Harvey et al., 2021, Nature Reviews Microbiology).

Other names

SARS-CoV-2 CD8+ T-cell epitopesSARS-CoV-2 HLA class I complexesCOVID-19 CTL epitopesSARS-CoV-2 MHC-I peptide complexSARS-CoV-2–derived CTL epitopes presented on human MHC class I molecules

Presentation of viral peptides to CD8+ T cells to induce targeted lysis of infected cells and establish immunological memory.