Identification of an immunodominant H-2Db-restricted CTL epitope of human PSA
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In: The Prostate, Vol. 64, No. 1, 15.06.2005, p. 50-59.
Research output: Journal contributions › Journal articles › Research › peer-review
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TY - JOUR
T1 - Identification of an immunodominant H-2Db-restricted CTL epitope of human PSA
AU - Pavlenko, Maxim
AU - Leder, Christoph
AU - Roos, Anna-Karin
AU - Levitsky, V.
AU - Pisa, Pavel
PY - 2005/6/15
Y1 - 2005/6/15
N2 - 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 C57B1/6 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.
AB - 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 C57B1/6 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.
KW - Biology
KW - prostate-specific antigen
KW - DNA vaccine
KW - CTL epitope
KW - Immunodominance
UR - http://www.scopus.com/inward/record.url?scp=19544385574&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/07d6a316-3f31-3ee6-bf1b-b6cb18bffe15/
U2 - 10.1002/pros.20221
DO - 10.1002/pros.20221
M3 - Journal articles
VL - 64
SP - 50
EP - 59
JO - The Prostate
JF - The Prostate
SN - 0270-4137
IS - 1
ER -