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Identification of HLA class I dependent immunogenic peptides from clonotypic TCRbeta expressed in cutaneous T-cell lymphoma.

Zeng J, Müller-Berghaus J, Nguyen XD, Klüter H, Schönhaber H, Song M, Schwinn N, Schadendorf D, Goerdt S, Eichmüller S, Dippel E

German Cancer Research Center, DKFZ, Skin Cancer Unit, Heidelberg, Germany.

The clonotypic T-cell receptor (TCR) is a potential target antigen for specific immunotherapy of cutaneous T-cell lymphoma (CTCL). We identified T-cell epitopes from the rearranged TCR beta chain of the malignant T-cell population by the "reverse immunology" approach. Peptide-specific T-cell lines were generated against predicted epitopes and tested for the recognition of tumor cells and cells transfected with the full-length DNA coding for TCRV beta chain. Two peptides derived from the clonotypic TCRVbeta of a HLA-A2 positive patient could induce peptide-specific T cells from peripheral blood mononuclear cells of healthy donors and the patient as assessed by IFN-gamma ELISpot assay. Furthermore, the reactive CTLs efficiently recognized autologous Sézary tumor cells, as well as HLA-A2 positive 293 cells transfected with recombinant plasmid expressing the corresponding TCRVbeta29 protein. Similar results were obtained in a HLA-A3+ patient for TCRVbeta7-Jbeta2.7. In conclusion, our experiments show that the TCR beta chain harbors epitopes suitable as targets for specific vaccination which might be a promising approach for the specific immunotherapy of cutaneous T-cell lymphoma patients.

Published 2 October 2006 in Int J Cancer, 119(10): 2476-80.
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