Definition of TCR epitopes for CTL-mediated attack of cutaneous T cell lymphoma |
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Authors: | Winter Dorian Fiebiger Edda Meraner Paul Auer Herbert Brna Christine Strohal Robert Trautinger Franz Knobler Robert Fischer Gottfried F Stingl Georg Maurer Dieter |
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Institution: | Division of Immunology, Allergy, and Infectious Diseases, Department of Dermatology, University of Vienna Medical School, Waehringer Guertel 189-20, A-1090 Vienna, Austria. |
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Abstract: | Therapeutic vaccination against cutaneous T cell lymphoma (CTCL) requires the characterization of cancer cell-specific CTL epitopes. Despite reported evidence for tumor-reactive cytotoxicity in CTCL patients, the nature of the recognized determinants remains elusive. The clonotypic TCR of CTCL cells is a promising candidate tumor-specific Ag. In this study, we report that the clonotypic and framework regions of the TCRs expressed in the malignant T cell clones of six CTCL patients contain multiple peptides with anchor residues fitting the patients' MHC class I molecules. We demonstrate that TCR peptide-specific T cells from the blood of healthy donors and patients can be induced to become cytotoxic effectors after repeated stimulation with 6 of 11 selected peptides with experimentally proven affinity for HLA-A*0201. Importantly, 4 of these 6 CTL lines reproducibly recognize and lyse autologous primary CTCL cells in MHC class I/CD8-dependent fashion. These tumoricidal CTL lines are directed against epitopes from V, hypervariable, and C regions of TCRalpha. We therefore conclude that recombined as well as V framework regions of the tumor cell TCRs contain predictable epitopes for CTL-mediated attack of CTCL cells. Our data further suggest that such peptides represent valuable tools for future anti-CTCL vaccination approaches. |
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