title: Tyrosinase epitope recognized by an HLA-DR-restricted T-cell line from a Vogt-Koyanagi-Harada disease patient.
abstract: 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 HLA-DR4 (DRB1(*)0405) and HLA-DR53 (DRB4(*)0101). Tyrosinase is a melanoma antigen (Ag) expressed by normal melanocytes as well as melanoma cells against which responses by autologous T cells have been detected. We established a T-cell line from the peripheral blood of a patient with VKH disease which responded to synthetic peptides corresponding to tyrosinase. The T-cell line was generated which recognized the tyrosinase p188 - 208 peptide when presented by the HLA-DR4 (DRB1(*)0405) molecule on the surface of HLA class II-expressing L-cell transfectants. The minimal 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 DRB1(*)0405-binding peptide motif (hydrophobic residues (Y, F, W) at position 1 as an anchor residue, and negatively charged residues (D, E) at position 9), which corresponded to the W at p195 and the D at p203. These observations demonstrate that tyrosinase peptides are immunogenic, and may be a candidate for an autoantigen in VKH disease, suggesting that probing the T-cell responses against synthetic peptides is a productive approach for identifying the autoantigenic peptides associated with autoimmune diseases including VKH disease.
authors.affiliation: Department of Pathology, Asahikawa Medical College, 4-5-3-11, Nishikagura, Asahikawa, 078, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Kokubo
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Miyokawa
authors.forename: S
authors.initials: S
authors.lastname: Kimura
authors.forename: R
authors.initials: R
authors.lastname: Kinouchi
authors.forename: M
authors.initials: M
authors.lastname: Katagiri
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014607:Uveomeningoencephalitic Syndrome / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D004247:DNA; D014442:Monophenol Monooxygenase