Chemical Complementarity of Tumor Resident, Adaptive Immune Receptor CDR3s and Previously Defined Hepatitis C Virus Epitopes Correlates with Improved Outcomes in Hepatocellular Carcinoma

Viral Immunol. 2023 Dec;36(10):669-677. doi: 10.1089/vim.2023.0078. Epub 2023 Dec 5.


To better understand how adaptive immune receptors (IRs) in hepatocellular carcinoma (HCC) microenvironments are related to disease outcomes, we employed a chemical complementarity scoring algorithm to quantify electrostatic complementarity between HCC tumor TRB or IGH complementarity-determining region 3 (CDR3) amino acid (AA) sequences and previously characterized hepatitis C virus (HCV) epitopes. High electrostatic complementarity between HCC-resident CDR3s and 12 HCV epitopes was associated with greater survival probabilities, as indicated by two distinct HCC IR CDR3 datasets. Two of the HCV epitopes, HCV*71871 (TRB) and HCV*13458 (IGH), were also determined to represent significantly larger electrostatic CDR3-HCV epitope complementarity in HCV-positive HCC cases, compared with HCV-negative HCC cases, with the CDR3s representing yet a third, independent HCC dataset. Overall, the results indicated the utility of CDR3 AA sequences as biomarkers for HCC patient stratification and as potential guides for the development of therapeutic reagents.

Keywords: CDR3-HCV antigen chemical complementarity; T cell receptor-beta; immunoglobulins; liver cancer.

MeSH terms

  • Carcinoma, Hepatocellular*
  • Complementarity Determining Regions / genetics
  • Epitopes
  • Hepacivirus
  • Hepatitis C*
  • Humans
  • Liver Neoplasms*
  • Tumor Microenvironment


  • Epitopes
  • Complementarity Determining Regions