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

• Published in: International immunology Vol. 13; no. 5; pp. 625 - 632
• Main Authors: Markiewicz, Mary A., Fallarino, Francesca, Ashikari, Andrew, Gajewski, Thomas F.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2001; Oxford Publishing Limited (England)
• Subjects: Animals; Antigen Presentation; Antigens, Neoplasm - administration & dosage; Antigens, Neoplasm - metabolism; APC antigen-presenting cells; Cancer Vaccines - immunology; Cancer Vaccines - pharmacology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; cross-priming; CTL cytotoxic T lymphocyte; cytotoxic T lymphocytes; DC dendritic cells; dendritic cells; EAE experimental autoimmune encephaleomyelitis; Epitopes - administration & dosage; Epitopes - metabolism; Female; Graft Rejection; Histocompatibility Antigens Class I - metabolism; IL-12; Interleukin-12 - administration & dosage; Mast-Cell Sarcoma - immunology; Mast-Cell Sarcoma - therapy; Mice; Mice, Inbred DBA; MLTC mixed lymphocyte tumor culture; Neoplasm Transplantation; NOD non-obese diabetic; PBMC peripheral blood mononuclear cells; Tumor Cells, Cultured; tumor immunity
• ISSN: 0953-8178; 1460-2377
• 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.