Identification of HLA-B27-restricted cytotoxic T lymphocyte epitope from carcinoembryonic antigen

Int J Cancer. 2002 Jan 1;97(1):58-63. doi: 10.1002/ijc.1579.

Abstract

Characterization of epitopes recognized by cytotoxic T lymphocytes (CTLs) in the sequence of tumor antigens is an important step in the development of tumor therapies. Because carcinoembryonic antigen (CEA) is a protein expressed in a high number of epithelial tumors, it is an interesting target to study. We screened for the presence of HLA-B27-restricted CTL epitopes from CEA by studying the binding to HLA-B27 of 31 synthetic peptides predicted to bind to this molecule. This afforded 16 peptides with moderate or high binding affinity. Immunization of HLA-B27 transgenic mice with the best binder peptides yielded 4 immunogenic peptides: CEA(9-17), CEA(9-18), CEA(138-146) and CEA(360-369). However, splenocytes from mice immunized with a vaccinia virus-expressing CEA recognized only CEA(9-18). These CTLs were of the CD8(+) phenotype, which upon stimulation with peptide specifically produced IFN-gamma. Moreover, they did not cross-react against peptides of region 9-18 from proteins of the CEA family. Our results show that CEA(9-18) may induce specific CTL responses against CEA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / immunology*
  • Cell Line
  • Cross Reactions
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-B27 Antigen / immunology*
  • Humans
  • Immunization
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Transgenic
  • Peptides / chemistry
  • Peptides / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccinia virus
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / immunology*

Substances

  • Carcinoembryonic Antigen
  • Epitopes, T-Lymphocyte
  • HLA-B27 Antigen
  • Peptides
  • beta 2-Microglobulin
  • Interferon-gamma