Induction of tumor-reactive T helper responses by a posttranslational modified epitope from tumor protein p53

Takumi Kumai, Kei Ishibashi, Kensuke Oikawa, Yoshinari Matsuda, Naoko Aoki, Shoji Kimura, Satoshi Hayashi, Masahiro Kitada, Yasuaki Harabuchi, Esteban Celis, Hiroya Kobayashi

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Posttranslational modifications regulate the function and stability of proteins, and the immune system is able to recognize some of these modifications. Therefore, the presence of posttranslational modifications increases the diversity of potential immune responses to a determinant antigen. The stimulation of tumor-specific CD4+ helper T lymphocytes (HTLs) is considered important for the production of anti-tumor antibodies by B cells and for the generation and persistence of CD8+ cytotoxic T lymphocytes, and in some instances, HTLs can directly reduce tumor cell growth. Identification of MHC class II-restricted peptide epitopes from tumor-associated antigens including those generated from posttranslational protein modifications should enable the improvement of peptide-based cancer immunotherapy. We describe here an MHC class II binding peptide from the tumor protein p53, which possesses an acetylated lysine at position 120 (p53110-124/AcK120) that is effective in eliciting CD4+ T cell responses specific for the acetylated peptide. Most importantly, the acetylated peptide-reactive CD4 HTLs recognized the corresponding naturally processed posttranslational modified epitope presented by either dendritic cells loaded with tumor cell lysates or directly on tumors expressing p53 and the restricting MHC class II molecules. Treatment of tumor cells with a histone deacetylase inhibitor augmented their recognition by the p53110-124/AcK120-reactive CD4+ T cells. These findings prove that the epitope p53110-124/AcK120 is immunogenic for anti-tumor responses and is likely to be useful for cancer immunotherapy.

Original languageEnglish (US)
Pages (from-to)469-478
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume63
Issue number5
DOIs
Publication statusPublished - May 2014

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Keywords

  • Acetylated lysine
  • CD4 T cell
  • Epitope
  • Immunotherapy
  • Posttranslational modification
  • p53

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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