Cytotoxic T lymphocytes that recognize decameric peptide sequences of retinoblastoma binding protein 1 (RBP-1) associated with human breast cancer

Br J Cancer. 1999 Sep;81(2):342-9. doi: 10.1038/sj.bjc.6690698.

Abstract

Retinoblastoma binding protein 1 (RBP-1) is a 143-kDa nuclear phosphoprotein that promotes cell growth by inhibiting the product of retinoblastoma tumour suppressor gene (pRB). We recently found that RBP-1 contains KASIFLK, a heptameric peptide (250-256) recognized by human antibodies and overexpressed by breast cancer cells. In the present study, we demonstrate that human T-cells stimulated with RBP-1 decameric peptides containing KASIFLK can kill human breast cancer cells. These decamers, GLQKASIFLK (247-256) and KASIFLKTRV (250-259), have anchor motifs for both HLA-A2 and HLA-A3. Peripheral blood lymphocytes from 41 normal donors were stimulated by these peptides in culture media containing 15 IU ml(-1) interleukin-2, 25 IU ml(-1) interleukin-7 and 500 IU ml(-1) granulocyte-macrophage colony-stimulating factor. Cytotoxic activity of the T-cells was assessed against autologous B lymphoblastoid cells pulsed with each peptide. Stimulation by GLQKASIFLK generated specific cytotoxic T lymphocyte (CTL) lines from HLA-A2, A3 donors, HLA-A2 donors and HLA-A3 donors. Stimulation with KASIFLKTRV generated specific CTL lines from HLA-A2 donors. No HLA-A2-, A3 CTL line showed specific cytotoxicity against these target cells. These CTL lines were also cytotoxic against HLA-A2 and HLA-A3 breast cancer cells but not against normal fibroblastoid cell lines, normal epidermal cell lines, or a melanoma cell line. RBP-1 peptide antigens may be of clinical significance as a potential peptide vaccine against human breast cancer.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / physiology*
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic*
  • HLA-A Antigens
  • Humans
  • Lymphocyte Activation
  • Retinoblastoma Protein / chemistry
  • Retinoblastoma Protein / physiology*
  • T-Lymphocytes, Cytotoxic / physiology*
  • Tumor Cells, Cultured

Substances

  • Carrier Proteins
  • HLA-A Antigens
  • Retinoblastoma Protein