Identification of a new HLA-A*0201-restricted T-cell epitope from the tyrosinase-related protein 2 (TRP2) melanoma antigen

For the development of peptide-based immunotherapies, the identification of additional tumor antigens and T-cell epitopes is required. Because HLA-A*0 201 is the most common allele in Caucasians, who represent the majority of patients with melanomas, 6 peptides carrying an HLA-A*0201 motif were synth esized from tyrosinase-related protein-2 (TRP2) melanoma antigen and tested for binding affinity to the HLA allele using processing-defective T2 cells . These peptides were then pulsed onto autologous dendritic cells and used to stimulate in vitro CD8(+)-enriched T cells isolated from peripheral bloo d of HLA-A*02(+) healthy donors or melanoma patients for the induction of s pecific cytotoxic T lymphocytes (CTLs), One peptide, TRP2(288-296) (SLDDYNH LV), the best HLA-A*0201 binder, elicited specific CTLs from 1 of 4 patient s and 3 of 4 healthy donors. The induced CTLs from the patient and from 1 d onor efficiently recognized HLA-A*02(+) TRP2(+) melanomas as well as COS-7 cells expressing HLA-A*0201 and TRP2 in an HLA class 1-restricted manner, a s assessed by cytokine production and direct cytolysis, The remaining 2 CTL lines derived from 2 donors displayed low T-cell receptor avidity, which c ould lyse melanoma cells in the presence of exogenous peptide. Since TRP2 i s an antigen expressed in most melanomas, identification of the TRP2/HLA-A* 0201 peptide SLDDYNHLV may facilitate the design of present peptide-based i mmunotherapies for the treatment of a large fraction of melanoma patients. Int. J. Cancer 87:399-404, 2000, (C) 2000 Wiley-Liss, Inc.