Identification of an immunodominant H‐2Db‐restricted CTL epitope of human PSA

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Abstract
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‐2b). 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‐2Db restricted epitope corresponding to the amino acid residues 65–74 (HCIRNKSVIL) of the protein. The CTLs had similar functional avidity against two putative H‐2Db 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‐2Db pentamers assembled with this peptide are an efficient tool for monitoring of PSA‐specific CTL responses after DNA vaccination.
Funding Information
  • Cancer Society, Stockholm
  • Swedish Cancer Society
  • Karolinska Institute Funds
  • EU 6-FP “ALLOSTEM” (LSHB-CT-2004-503319)
  • US Department of Defense Prostate Cancer Research Program (PC030958)