Recognition of HLA-A2-restricted mammaglobin-A-derived epitopes by CD8+ cytotoxic T lymphocytes from breast cancer patients

Breast Cancer Res Treat. 2004 Nov;88(1):29-41. doi: 10.1007/s10549-004-8918-1.


A breast cancer-associated antigen, mammaglobin-A, is specifically expressed in 80% of primary breast tumors. The definition of immune responses against this highly expressed breast cancer-specific antigen should be of great value in the development of new therapeutic strategies for breast cancer. Thus, the purpose of this study was to identify HLA-A2-restricted mammaglobin-A-derived epitopes recognized by CD8+ cytotoxic T lymphocytes (CTL). We identified seven mammaglobin-A-derived candidate epitopes that bind the HLA-A2 molecule (Mam-A2.1-7) by means of a HLA class I-peptide binding computer algorithm from the Bioinformatics & Molecular Analysis Section of the National Institutes of Health. Subsequently, we determined that CD8+ CTLs from breast cancer patients reacted to the Mam-A2.1 (83-92, LIYDSSLCDL), Mam-A2.2 (2-10, KLLMVLMLA), Mam-A2.3 (4-12, LMVLMLAAL), Mam-A2.4 (66-74, FLNQTDETL), and Mam-A2.7 (32-40, TINPQVSKT) epitopes using an IFN-gamma ELISPOT assay. Interestingly, healthy individuals also showed high reactivity to the Mam-A2.2 epitope. Two CD8+ CTL lines generated in vitro against TAP-deficient T2 cells loaded with the candidate epitopes showed significant cytotoxic activity against the Mam-A2.1-4 epitopes. These CD8+CTL lines recognized a HLA-A2+breast cancer cell line expressing the Mam-A2.1 epitope. In addition, DNA vaccination of HLA-A2+/human CD8+ double-transgenic mice with a DNA construct encoding the Mam-A2.1 epitope and the HLA-A2 molecule induced a significant expansion of epitope-specific CD8+ CTLs that recognize the same HLA- A2+/Mam-A2.1+ breast cancer cell line. In conclusion, these results demonstrate the immunotherapeutic potential of mammaglobin-A for the treatment and prevention of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Animals
  • Antigens, Neoplasm
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Epitopes
  • Female
  • HLA-A2 Antigen / analysis
  • Humans
  • Immunotherapy / methods
  • Mammaglobin A
  • Mice
  • Mice, Transgenic
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / immunology*
  • Neoplasms, Experimental
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured
  • Uteroglobin / analysis
  • Uteroglobin / immunology*
  • Vaccines, DNA


  • Antigens, Neoplasm
  • Epitopes
  • HLA-A2 Antigen
  • Mammaglobin A
  • Neoplasm Proteins
  • SCGB2A2 protein, human
  • Vaccines, DNA
  • Uteroglobin