Epitope spreading upon P815 tumor rejection triggered by vaccination with the single class I MHC-restricted peptide P1A

Int Immunol. 2001 May;13(5):625-32. doi: 10.1093/intimm/13.5.625.


Epitope spreading has been best characterized as an exacerbating factor in CD4(+) T cell-dependent autoimmune disease models and is believed to occur via presentation of antigens liberated by tissue destruction initiated by CD4(+) T cells specific for a primary epitope. The growing evidence that exogenous antigens can also be processed and presented by class I MHC molecules has suggested that epitope spreading could occur for CD8(+) cytotoxic T lymphocyte (CTL) responses as well. In the context of anti-tumor immunity, expansion of a CTL response to include secondary epitopes could improve the efficacy of therapeutic vaccines. To determine directly whether epitope spreading can occur during an anti-tumor immune response, two defined class I MHC-binding peptides in the P815 tumor model were utilized. We observed that immunization against the single tumor peptide, P1A, followed by rejection of a P1A(+) tumor, subsequently yielded CTL activity and tumor protection against a P1A(-) tumor variant. P1A immunized mice that subsequently rejected tumor challenge developed CTL against a second defined epitope, P1E. These results indicate that, as for class II-restricted peptides in autoimmune disease, epitope spreading can occur for class I-restricted peptides during tumor rejection. A broadened CTL response may help eliminate outgrowth of antigen-negative tumor variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Neoplasm / administration & dosage*
  • Antigens, Neoplasm / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology
  • Cancer Vaccines / pharmacology
  • Epitopes / administration & dosage
  • Epitopes / metabolism
  • Female
  • Graft Rejection
  • Histocompatibility Antigens Class I / metabolism
  • Interleukin-12 / administration & dosage
  • Mast-Cell Sarcoma / immunology*
  • Mast-Cell Sarcoma / therapy
  • Mice
  • Mice, Inbred DBA
  • Neoplasm Transplantation
  • Tumor Cells, Cultured


  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes
  • Histocompatibility Antigens Class I
  • tumor rejection antigen P815A, mouse
  • Interleukin-12