Identification of a 17beta-hydroxysteroid dehydrogenase type 12 pseudogene as the source of a highly restricted BALB/c Meth A tumor rejection peptide.
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 17beta-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 Hsd17b12(114-122) with threonine instead of isoleucine at codon 114 and is designated Hsd17b12(114T). Immunization of mice with an Hsd17b12(114T) peptide-pulsed dendritic cell-based vaccine or a non-viral plasmid construct expressing the Hsd17b12(114T) peptide protected the mice from lethal Meth A tumor challenge in tumor rejection assays. A Hsd17b12(114-122) 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.
Hendrickson
Ronald C
RC
Department of Chemistry, University of Virginia, Charlottesville, VA 22901, USA.
Cicinnati
Vito R
VR
Albers
Andreas
A
Dworacki
Grzegorz
G
Gambotto
Andrea
A
Pagliano
Ornella
O
Tüting
Thomas
T
Mayordomo
Jose I
JI
Visus
Carmen
C
Appella
Ettore
E
Shabanowitz
Jeffrey
J
Hunt
Donald F
DF
DeLeo
Albert B
AB
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006649:Histocompatibility Antigens / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011544:Pseudogenes / Q000276:immunology*; D012513:Sarcoma, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006649:Histocompatibility Antigens; D010455:Peptides; C029237:tumor-associated transplantation antigen; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase