TYROSINASE EPITOPE RECOGNIZED BY AN HLA-DR-RESTRICTED T-CELL LINE FROM A VOGT-KOYANAGI-HARADA DISEASE PATIENT

Human T-cell-mediated autoimmune diseases are often genetically linked to particular alleles of HLA class II genes. Vogt-Koyanagi-Harada's ( VKH) disease, which is regarded as an autoimmune disorder in multiple organs containing melanocytes, has been found to be associated with HL A-DR4 (DRB10405) and HLA-DR53 (DRB4*0101). Tyrosinase is a melanoma a ntigen (Ag) expressed by normal melanocytes as well as melanoma cells against which responses by autologous T cells have been detected. We e stablished a T-cell line from the peripheral blood of a patient with V KH disease which responded to synthetic peptides corresponding to tyro sinase. The T-cell line was generated which recognized the tyrosinase pl 88-208 peptide when presented by the HLA-DR4 (DRB10405) molecule o n the surface of HLA class II-expressing L-cell transfectants. The min imal antigenic peptide which induced T-cell responses was an 11-amino- acid sequence and located at tyrosinase p193-203 (E-I-W-R-D-I-D-F-A-H- E). This peptide contained the DRB10405-binding peptide motif (hydrop hobic residues (Y, F, W) at position 1 as an anchor residue, and negat ively charged residues (D, E) at position 9), which corresponded to th e W at p195 and the D at p203. These observations demonstrate that tyr osinase peptides are immunogenic, and may be a candidate for an autoan tigen in VKH disease, suggesting that probing the T-cell responses aga inst synthetic peptides is a productive approach for identifying the a utoantigenic peptides associated with autoimmune diseases including VK H disease.