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Dorian Winter, Edda Fiebiger, Paul Meraner, Herbert Auer, Christine Brna, Robert Strohal, Franz Trautinger, Robert Knobler, Gottfried F Fischer, Georg Stingl, Dieter Maurer, Definition of TCR Epitopes for CTL-Mediated Attack of Cutaneous T Cell Lymphoma, The Journal of Immunology, Volume 171, Issue 5, September 2003, Pages 2714–2724, https://doi.org/10.4049/jimmunol.171.5.2714
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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 TCRα. 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.
