Tumor-specific cytotoxic T cell clones from patients with breast and pancreatic adenocarcinoma recognize EBV-immortalized B cells transfected with polymorphic epithelial mucin complementary DNA

J Immunol. 1993 Aug 1;151(3):1654-62.

Abstract

Human breast and pancreatic adenocarcinomas are tumors of ductal epithelial cell origin and as such produce and express on their surface polymorphic epithelial cell mucin encoded by the MUC 1 gene. We have previously reported that tumor-specific cytotoxic T cells derived from patients bearing such tumors recognize specific epitopes on the mucin polypeptide core. This recognition was not MHC-restricted because of the highly repetitive sequence of the polypeptide core, which allows simultaneous recognition of many identical epitopes, and cross-linking and aggregation of TCR on mucin-specific T cells. Those studies were performed with limited numbers of tumor cells or allogeneic tumor cell lines. A renewable source of autologous cells presenting this Ag was necessary to further explore mucin-specific immunity. We report here successful establishment and functional analysis of mucin-specific CTL lines and clones derived from breast and pancreatic cancer patients, using either autologous or allogeneic mucin-transfected B cells as Ag. Our results demonstrate that transfection of autologous or allogeneic B cells with mucin confers upon them tumor Ag-presenting ability as well as susceptibility to lysis by mucin-specific CTL. Transfection of APC with this or any other human tumor Ag that may be molecularly defined in the future provides a unique and powerful tool with which to examine the ability of a tumor-associated Ag to stimulate T cell responses.

Publication types

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

MeSH terms

  • Adenocarcinoma / immunology*
  • Amino Acid Sequence
  • Antigen-Presenting Cells / immunology
  • Antigens, Neoplasm / immunology*
  • B-Lymphocytes / immunology
  • Breast Neoplasms / immunology*
  • Cell Transformation, Viral
  • Clone Cells
  • Cloning, Molecular
  • Cytotoxicity, Immunologic*
  • Herpesvirus 4, Human
  • Humans
  • Immunity, Cellular*
  • In Vitro Techniques
  • Molecular Sequence Data
  • Mucins / chemistry
  • Mucins / genetics
  • Mucins / immunology*
  • Pancreatic Neoplasms / immunology*
  • Peptides / chemistry
  • Peptides / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection

Substances

  • Antigens, Neoplasm
  • Mucins
  • Peptides