Identification of HLA class I dependent immunogenic peptides from clonotypic TCRbeta expressed in cutaneous T-cell lymphoma.
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.
Zeng
Jinyang
J
German Cancer Research Center, DKFZ, Skin Cancer Unit, Heidelberg, Germany.
Müller-Berghaus
Jan
J
Nguyen
Xuan Duc
XD
Klüter
Harald
H
Schönhaber
Hiltrud
H
Song
Mingxia
M
Schwinn
Nicole
N
Schadendorf
Dirk
D
Goerdt
Sergij
S
Eichmüller
Stefan
S
Dippel
Edgar
E
D000939:Epitopes / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic; D015789:HLA-A2 Antigen / Q000378:metabolism; D015791:HLA-A3 Antigen / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology* / Q000628:therapy; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D012751:Sezary Syndrome / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy
D000939:Epitopes; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta