Definition of TCR epitopes for CTL-mediated attack of cutaneous T cell lymphoma.
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.
Winter
Dorian
D
Division of Immunology, Allergy, and Infectious Diseases, Department of Dermatology, University of Vienna Medical School, Waehringer Guertel 189-20, A-1090 Vienna, Austria.
Fiebiger
Edda
E
Meraner
Paul
P
Auer
Herbert
H
Brna
Christine
C
Strohal
Robert
R
Trautinger
Franz
F
Knobler
Robert
R
Fischer
Gottfried F
GF
Stingl
Georg
G
Maurer
Dieter
D
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D010450:Endopeptidases / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell / Q000097:blood / Q000201:enzymology / Q000276:immunology* / Q000517:prevention & control; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000097:blood / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000097:blood / Q000201:enzymology / Q000276:immunology* / Q000517:prevention & control; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D010450:Endopeptidases