International Immunology, Vol. 13, No. 5, 625-632,
May 2001
© 2001 Japanese Society for Immunology
Epitope spreading upon P815 tumor rejection triggered by vaccination with the single class I MHC-restricted peptide P1A
1 Departments of Pathology,
2 Surgery and
3 Medicine, and
4 Committee on Immunology, University of Chicago, 5841 South Maryland Avenue, MC2115, Chicago, IL 60637, USA
Correspondence to: T. F. Gajewski, 5841 South Maryland Avenue, MC2115, Chicago, IL 60637, USA
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.
Keywords: cross-priming, cytotoxic T lymphocytes, dendritic cells, IL-12, tumor immunity
Transmitting editor: J. Banchereau
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