Identification of an immunodominant H-2D(b)-restricted CTL epitope of human PSA.
BACKGROUND
Human prostate specific antigen (PSA) is expressed selectively in prostate epithelium and is a potential target for the immunotherapy against prostate cancer. Various PSA-based vaccines have been reported to induce cytotoxic T lymphocyte (CTL) responses in animal models. Here, we present the identification and validation of an immunodominant CTL epitope of PSA in C57Bl/6 mice (H-2(b)).


METHODS
PSA-specific CTLs were induced by immunization with a plasmid expressing PSA. Epitope specificity of the CTLs was determined by their reactivity against a panel of C-terminus truncated or mutated PSA proteins and use of bioinformatical prediction with the SYFPEITHI algorithm.


RESULTS
The majority of PSA-specific CTLs were directed against a single H-2D(b) restricted epitope corresponding to the amino acid residues 65-74 (HCIRNKSVIL) of the protein. The CTLs had similar functional avidity against two putative H-2D(b) binding peptides: a 9-aa-long psa65-73 (HCIRNKSVI) and a 10-aa-long psa65-74 (HCIRNKSVIL).


CONCLUSIONS
We demonstrate that the psa65-73 peptide can be used for reactivation of PSA-specific CTLs in vitro and ex vivo, and H-2D(b) pentamers assembled with this peptide are an efficient tool for monitoring of PSA-specific CTL responses after DNA vaccination.
Pavlenko
Maxim
M
Department of Oncology and Pathology, Cancer Center Karolinska, Immune and Gene Therapy Laboratory, Karolinska Institute, Stockholm, Sweden. maxim.pavlenko@cck.ki.se
Leder
Christoph
C
Roos
Anna-Karin
AK
Levitsky
Victor
V
Pisa
Pavel
P
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology; D017353:Gene Deletion; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010957:Plasmids; D017430:Prostate-Specific Antigen / Q000235:genetics* / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology
D019496:Cancer Vaccines; D016056:Immunodominant Epitopes; D019444:Vaccines, DNA; D017430:Prostate-Specific Antigen