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Immunology |
Institute for Immunology [M. S., P. D., B. W., F. S., E. P. R.] and Department of Surgery [D. O.], Medical Faculty, Technical University of Dresden, 01101 Dresden, and Department of Immunology, Institute for Cell Biology, University of Tuebingen, 72076 Tuebingen [S. S., H-G. R.], Germany
The identification of tumor-associated antigens recognized by CD8+ cytotoxic T cells paved the way to new concepts in adjuvant anticancer therapy. However, the number of tumor-associated proteins found to be expressed in the majority of human cancers is still rather limited. Recently, the newly identified apoptosis inhibitor protein survivin has been recognized as a widely occurring tumor-associated protein. In the present study, we demonstrate that survivin is capable of inducing specific CD8+ effector T cells in vitro. T cells from healthy donors were subjected to several cycles of stimulation by autologous dendritic cells (DCs) pulsed with soluble recombinant survivin protein. Activation of CD8+ cytotoxic T cells by survivin-derived peptides cross-presented by DCs was demonstrated by lysis of autologous survivin-expressing B cell transfectants. Using a peptide-motif scoring system, two survivin peptides (ELTLGEFLKL and TLPPAWQPFL) were predicted and proved to bind to the HLA-A*0201 molecule. Both peptides were shown to induce CD8+ effector T cells when presented on DCs; one peptide could be verified to result from natural intracellular processing of survivin. These findings recommend survivin as a new and widely applicable target for protein- and peptide-based immunotherapy of tumors.
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