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

Abstract:

: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.

journal_name

J Clin Immunol

authors

Ripberger E,Linnebacher M,Schwitalle Y,Gebert J,von Knebel Doeberitz M

doi

10.1023/a:1025329819121

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

415-23

issue

5

eissn

0271-9142

issn

1573-2592

journal_volume

23

pub_type

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