Epitope spreading upon P815 tumor rejection triggered by vaccination with the single class I MHC-restricted peptide P1A.
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.
Markiewicz
M A
MA
Department of Pathology, University of Chicago, 5841 South Maryland Avenue, MC2115, Chicago, IL 60637, USA.
Fallarino
F
F
Ashikari
A
A
Gajewski
T F
TF
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology; D000939:Epitopes / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D006084:Graft Rejection; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D018664:Interleukin-12 / Q000008:administration & dosage; D012515:Mast-Cell Sarcoma / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; C076546:tumor rejection antigen P815A, mouse; D018664:Interleukin-12