Identification of a 17β-hydroxysteroid dehydrogenase type 12 pseudogene as the source of a highly restricted BALB/c Meth A tumor rejection peptide

Abstract

Mass spectrometric analysis identified the peptide recognized by a cytotoxic T lymphocyte (CTL) specific for the chemically induced BALB/c Meth A sarcoma as derived from a 17β-hydroxysteroid dehydrogenase type 12 (Hsd17b12) pseudogene present in the BALB/c genome, but only expressed in Meth A sarcoma. The sequence of the peptide is TYDKIKTGL and corresponds to Hsd17b12114-122 with threonine instead of isoleucine at codon 114 and is designated Hsd17b12114T. Immunization of mice with an Hsd17b12114T peptide-pulsed dendritic cell-based vaccine or a non-viral plasmid construct expressing the Hsd17b12114T peptide protected the mice from lethal Meth A tumor challenge in tumor rejection assays. A Hsd17b12114-122 peptide-pulsed vaccine was ineffective in inducing resistance in mice to Meth A sarcoma. These results confirm the immunogenicity of the identified tumor peptide, as well as demonstrate the efficacies of these vaccine vehicles. These findings suggest that the role of the human homolog of Hsd17b12, HSD17B12, as a potential human tumor antigen be explored. © 2009 Springer-Verlag.