Induction of HLA-A2-restricted CTLs to the mucin 1 human breast cancer antigen

J Immunol. 1997 Dec 1;159(11):5211-8.


HLA-A*0201/Kb transgenic mice were immunized with oxidized mannan-mucin 1 (MUC1) as a fusion protein (containing five repeats of the 20-amino-acid MUC1 VNTR (variable number of tandem repeats) that generated highly active CD8+ CTLs to MUC1 peptides. In a direct CTL assay, the MUC1 peptides could be presented specifically by both the transgenic murine HLA-A*0201/Kb and human HLA-A*0201 molecules. The 9-mer MUC1 peptide sequences (APDTRPA and STAPPAHGV) were presented by HLA-A*0201, although they did not contain L at P2 and L/V at P9, the preferred motifs; as a consequence, the binding was of relatively low affinity when compared with a high affinity-binding HIV peptide (ILKEPVHGV). In addition, when mice were immunized separately with the HLA-A*0201-binding peptides (STAPPAHGV or APDTRPAP-containing peptides-keyhole limpet hemocyanin-mannan), direct lysis of MCF-7 (HLA-A*0201+, MUC1+) also occurred. The findings are of interest for tumor immunotherapy, particularly as the CTLs generated to low affinity-binding peptides were highly active and could specifically lyse an HLA-A*0201+ human breast cancer cell line without further in vitro stimulation. The findings demonstrate that the range of peptides that can generate CTLs is broader than formerly considered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation*
  • Breast Neoplasms / immunology*
  • Cytotoxicity Tests, Immunologic
  • Epitopes
  • HLA-A2 Antigen / immunology*
  • Humans
  • Mice
  • Mice, Transgenic
  • Minisatellite Repeats
  • Molecular Sequence Data
  • Mucin-1 / immunology*
  • Peptides
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured


  • Epitopes
  • HLA-A2 Antigen
  • Mucin-1
  • Peptides