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.