title: Generation of survivin-specific CD8+ T effector cells by dendritic cells pulsed with protein or selected peptides.
abstract: 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 (ELTLGE-FLKL 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.
authors.affiliation: Institute for Immunology, Medical Faculty, Technical University of Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmitz
authors.forename: P
authors.initials: P
authors.lastname: Diestelkoetter
authors.forename: B
authors.initials: B
authors.lastname: Weigle
authors.forename: F
authors.initials: F
authors.lastname: Schmachtenberg
authors.forename: S
authors.initials: S
authors.lastname: Stevanovic
authors.forename: D
authors.initials: D
authors.lastname: Ockert
authors.forename: H G
authors.initials: HG
authors.lastname: Rammensee
authors.forename: E P
authors.initials: EP
authors.lastname: Rieber
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D011506:Proteins / Q000276:immunology* / Q000378:metabolism; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
chemical_list: C107489:BIRC5 protein, human; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011506:Proteins; D000077022:Survivin