Identification of an HLA-A0201-restricted CTL epitope generated by a tumor-specific frameshift mutation in a coding microsatellite of the OGT gene

J Clin Immunol. 2003 Sep;23(5):415-23. doi: 10.1023/a:1025329819121.


Deficient DNA mismatch repair results in microsatellite instability and might induce shifts of translational reading frames of genes encompassing coding microsatellites. These may be translated in truncated proteins, including neo-peptide tails functioning as tumor rejection antigens, when presented in the context of MHC class I. Recently, others and we identified a frameshift mutation in the coding T(10) microsatellite of the O-linked N-acetylglucosamine transferase gene (OGT) occuring in up to 41% of microsatellite unstable colorectal cancers. Here we describe a novel HLA-A0201-restricted cytotoxic T lymphocyte (CTL)-epitope (28-SLYKFSPFPL; FSP06) derived from this mutant OGT-protein. FSP06-specific CTL-clones killed peptide-sensitized target cells and tumor cell lines expressing both HLA-A0201 and mutant OGT proteins. This demonstrates that FSP06 is endogenously expressed and represents a CD8(+)-T cell epitope. Our data corroborate the concept of frameshift peptides constituting a novel subset of tumor-associated antigens specifically encountered in cancer cells with deficient mismatch repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens / chemistry
  • Antigens / immunology
  • B-Lymphocytes / immunology
  • Cell Line, Tumor
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Epitopes, T-Lymphocyte / immunology*
  • Frameshift Mutation / genetics*
  • HLA-A Antigens / immunology*
  • HLA-A2 Antigen
  • Humans
  • Microsatellite Repeats / genetics*
  • N-Acetylglucosaminyltransferases / chemistry
  • N-Acetylglucosaminyltransferases / genetics*
  • N-Acetylglucosaminyltransferases / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*


  • Antigens
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • N-Acetylglucosaminyltransferases
  • UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase