Human Leukocyte Antigen A*02:01 (HLA-A*02:01) presenting Hepatitis C Virus Non-Structural protein 3 (HCV NS3) peptide 1073-1081 (CINGVCWTV) (HLA-A*02:01/HCV NS3-1073)

The Human Leukocyte Antigen A*02:01 (HLA-A*02:01) presenting Hepatitis C Virus Non-Structural protein 3 (HCV NS3) peptide 1073-1081 is a specific peptide-major histocompatibility complex (pMHC) found on the surface of hepatocytes infected with the Hepatitis C Virus (Sautto et al., 2016, PubMed: 26854034). This complex consists of the HLA-A*02:01 molecule presenting a highly conserved 9-amino acid epitope, CINGVCWTV, derived from the viral NS3 protein at position 1073 (IEDB Epitope ID: 7465). In the context of natural infection, this complex is recognized by endogenous CD8+ T cells, playing a critical role in the immune response against HCV (Spear et al., 2016, PubMed: 27163105). Because this epitope is immunodominant and relatively conserved across HCV genotype 1, it has become a primary target for adoptive T-cell therapies, particularly T-cell receptor (TCR) engineered T cells. These therapeutic approaches aim to bypass natural immune exhaustion or failure in chronic HCV patients by providing high-affinity TCRs that specifically recognize the NS3-1073/HLA-A2 complex. Targeting this pMHC allows for the precise elimination of infected cells while minimizing damage to healthy tissue, although risks of cross-reactivity with similar self-peptides remain a significant safety consideration (Pasetto et al., 2017, PubMed: 28416633).

Other names

HLA-A*02:01/NS3-1073HLA-A2/CINGVCWTVHCV NS3 1073-1081 pMHCA2/NS3-1073

Targeted T-cell mediated cytotoxicity via specific TCR binding to the peptide-MHC complex, triggering the release of perforin and granzymes to induce apoptosis in infected cells (Sautto et al., 2016).