Identification of immunodominant HLA-B7-restricted CD8+ cytotoxic T cell epitopes derived from mammaglobin-A expressed on human breast cancers

Breast Cancer Res Treat. 2011 May;127(1):81-9. doi: 10.1007/s10549-010-0975-z. Epub 2010 Jun 11.


Mammaglobin-A (MGBA), a 10-kD protein, is over expressed in 80% of primary and metastatic human breast cancers. Breast cancer patients demonstrate high frequencies of CD8(+) cytotoxic T lymphocytes (CTL) specific to MGBA. Defining CD8(+) CTL responses to HLA class I-restricted MGBA-derived epitopes assumes significance in the context of our ongoing efforts to clinically translate vaccine strategies targeting MGBA for prevention and/or treatment of human breast cancers. In this study, we define the CD8(+) CTL response to MGBA-derived candidate epitopes presented in the context of HLA-B7, which has a frequency of 17.7% in Caucasian and 15.5% in African American populations. We identified seven MGBA-derived candidate epitopes with high predicted binding scores for HLA-B7 using a computer algorithm. Membrane stabilization studies with TAP-deficient T2 cells transfected with HLA-B7 indicated that MGBA B7.3 (VSKTEYKEL), B7.6 (KLLMVLMLA), B7.7 (NPQVSKTEY), and B7.1 (YAGSGCPLL) have the highest HLA-B7 binding affinities. Further, two CD8(+) CTL cell lines generated in vitro against T2.B7 cells individually loaded with MGBA-derived candidate epitopes showed significant cytotoxic activity against MGBA B7.1, B7.3, B7.6, and B7.7. In addition, the same CD8(+) CTL lines lysed the HLA-B7(+)/MGBA(+) human breast cancer cell line DU-4475 but had no significant cytotoxicity against HLA-B7(-) or MGBA(-) breast cancer cell lines. Cold-target inhibition studies strongly suggest that MGBA B7.3 is an immunodominant epitope. In summary, our results define HLA-B7-restriced, MGBA-derived, CD8(+) CTL epitopes with all of the necessary features for developing novel vaccine strategies against HLA-B7 expressing breast cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibody Affinity / immunology
  • Antibody Specificity / immunology
  • Breast Neoplasms / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • HLA-B7 Antigen / immunology*
  • Humans
  • Mammaglobin A
  • Neoplasm Proteins / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Uteroglobin / immunology*


  • Antibodies, Monoclonal
  • Epitopes, T-Lymphocyte
  • HLA-B7 Antigen
  • Mammaglobin A
  • Neoplasm Proteins
  • SCGB2A2 protein, human
  • Uteroglobin