Identification of an HLA-A*24:02-restricted α-fetoprotein signal peptide-derived antigen and its specific T-cell receptor for T-cell immunotherapy

Immunology. 2020 Apr;159(4):384-392. doi: 10.1111/imm.13168. Epub 2020 Jan 10.


Hepatocellular carcinoma (HCC) is the most common type of liver cancer with limited treatments. Asia has the highest HCC incidence rates; China accounts for over 50% of all HCC cases worldwide. T-cell receptor (TCR) -engineered T-cell immunotherapies specific for human leukocyte antigen (HLA) -A*02:01-restricted α-fetoprotein (AFP) peptide have shown encouraging results in clinics. HLA-A*24:02 is more common than HLA-A*02:01 in Asian countries, including China. Here we identified a novel HLA-A*24:02-restricted peptide KWVESIFLIF (AFP2-11 ) located in AFP signal peptide domain by mass spectrometric analysis of HLA-bound peptides from HepG2 cells. A TCR (KWV3.1) specific for AFP2-11 -HLA-A*24:02 was isolated from peripheral blood mononuclear cells of a healthy donor. The binding affinity of soluble KWV3.1 to its antigen was determined to be ~55 μm, within the affinity range of native TCRs for self-antigens. KWV3.1-transfected T cells could specifically activate and kill AFP2-11 pulsed T2-A24 cells and AFP+ HLA-A*24:02+ tumor cell lines, demonstrating that AFP2-11 can be naturally presented on the surface of AFP+ tumor cell lines. The newly identified antigenic peptide can provide a novel target for immunotherapeutic strategies for patients with AFP+ HLA-A*24:02+ HCC.

Keywords: HLA-A*24:02; T-cell immunotherapy; hepatocellular carcinoma; mass spectrometry; α-fetoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Binding Sites
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy
  • Cell Line, Tumor
  • Coculture Techniques
  • Gene Expression
  • HLA-A24 Antigen / chemistry
  • HLA-A24 Antigen / genetics
  • HLA-A24 Antigen / immunology*
  • Healthy Volunteers
  • Hep G2 Cells
  • Humans
  • Immunotherapy / methods
  • Liver Neoplasms / genetics
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy
  • Oligopeptides / chemistry
  • Oligopeptides / genetics
  • Oligopeptides / immunology*
  • Protein Binding
  • Protein Sorting Signals / genetics*
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology
  • Transfection
  • alpha-Fetoproteins / chemistry
  • alpha-Fetoproteins / genetics
  • alpha-Fetoproteins / immunology*


  • AFP protein, human
  • Antigens, Neoplasm
  • HLA-A*24:02 antigen
  • HLA-A24 Antigen
  • Oligopeptides
  • Protein Sorting Signals
  • Receptors, Antigen, T-Cell
  • alpha-Fetoproteins