Journal
JOURNAL OF CLINICAL IMMUNOLOGY
Volume 23, Issue 5, Pages 415-423Publisher
KLUWER ACADEMIC/PLENUM PUBL
DOI: 10.1023/A:1025329819121
Keywords
microsatellite instability; frameshift peptides; tumor antigens; DNA mismatch repair; T-cell epitopes
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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.
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