Target intelligence / Profile preview

Hepatitis C virus-specific CD8+ T cell receptor (HCV-specific TCR)

Target
HCV-specific TCR
Molecular classification
Receptor, T cell receptor, Heterodimeric protein, Immune cell receptor
01

Overview

Hepatitis C virus-specific CD8+ T cell receptors (TCRs) are specialized heterodimeric proteins located on the surface of cytotoxic T lymphocytes that play a pivotal role in identifying and eliminating cells infected with the Hepatitis C virus (HCV). These receptors recognize specific viral peptide fragments, such as those from the NS3 or NS5B proteins, which are presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, most commonly HLA-A*02:01 (Wedemeyer et al., 2002, J. Immunol). Upon successful binding, the TCR triggers a signaling cascade that results in the release of cytotoxic molecules like granzymes and perforins, as well as antiviral cytokines such as interferon-gamma, to clear the infection (Neumann-Haefelin et al., 2005, Hepatology). In chronic HCV cases, the virus often evades this immune pressure through the selection of escape mutations within the targeted epitopes or by inducing T-cell exhaustion (Klenerman & Hill, 2005, Nat Rev Immunol). To counteract this, researchers are developing TCR-engineered T-cell (TCR-T) therapies, which involve modifying a patient's T cells to express high-affinity HCV-specific TCRs to treat chronic infection and HCV-associated hepatocellular carcinoma (Pasetto et al., 2017, Gastroenterology). This therapeutic approach aims to provide a precise and potent immune response capable of overcoming the limitations of the endogenous T-cell repertoire (Sautto et al., 2016, World J Gastroenterol).

Other names
HCV-specific T-cell receptorCD8+ T-cell receptor recognizing HCV peptidesHepatitis C virus-specific TCRHCV-specific CTL receptor
02

Mechanism of action

Recognition of specific HCV-derived peptides (e.g., NS3 1073-1081) presented by HLA-A*02:01 molecules, leading to T-cell activation and targeted destruction of infected hepatocytes.

03

Biological functions

Immune responseAntigen recognitionCell-mediated immunityCytotoxicityCytokine production
04

Disease associations

InfectionHepatitis CHepatocellular carcinomaLiver cirrhosisChronic inflammation
05

Safety considerations

Off-target toxicity due to cross-reactivity with self-antigensCytokine release syndrome (CRS)Viral mutational escape (epitope shifting)AutoimmunityOn-target off-tumor toxicity
06

Interacting drugs

TCR-engineered T cells

4 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeHCV RNA viral loadNS3-1073 epitope expressionAlanine aminotransferase (ALT) levelsInterferon-gamma levels

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