Hepatitis C virus non-structural protein 3 (1406-1415) peptide presented by Human Leukocyte Antigen A*02:01 (HCV NS3 (1406-1415)/HLA-A*02:01)

The HCV NS3:1406-1415 peptide presented by HLA-A*0201 is a specific peptide-major histocompatibility complex (pMHC) class I epitope derived from the Hepatitis C Virus (HCV) non-structural protein 3 (NS3). The peptide sequence, KLVALGINAV, is an immunodominant epitope recognized by CD8+ cytotoxic T lymphocytes (CTLs) in individuals carrying the HLA-A*02:01 allele (PubMed: 21411743). This complex is formed when the viral protein is proteolytically processed and the resulting decamer peptide is loaded onto HLA-A*02:01 molecules in the endoplasmic reticulum before being displayed on the cell surface (UniProt: P26664). Its biological role is to facilitate the immune surveillance of hepatocytes, where the presence of this pMHC complex triggers CTL-mediated apoptosis of the infected cell (PubMed: 15141013). In the context of chronic infection, this target is utilized in the development of TCR-engineered T-cell therapies and therapeutic vaccines, such as TG4040, which aim to overcome T-cell exhaustion and viral persistence (PubMed: 22434161). However, the high mutation rate of HCV can lead to viral escape through amino acid substitutions within the 1406-1415 sequence, rendering the complex unrecognizable to specific TCRs (PubMed: 11223734). Therapeutic strategies must therefore account for both the HLA restriction of the target and the potential for off-target cross-reactivity with similar self-peptides (PubMed: 25692555).

Other names

KLVALGINAV-HLA-A*02:01 complexHCV NS3 1406 epitopeNS3-1406/A2 complexHepatitis C virus NS3 (1406-1415) peptide-MHC complex

Recognition by specific T-cell receptors (TCRs) on CD8+ T cells, triggering the release of perforins and granzymes to induce apoptosis in infected cells.