Tyrosinase epitope recognized by an HLA-DR-restricted T-cell line from a Vogt-Koyanagi-Harada disease patient |
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Authors: | H Kobayashi T Kokubo Michinari Takahashi Keisuke Sato Naoyuki Miyokawa Shoji Kimura Reiko Kinouchi Makoto Katagiri |
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Institution: | (1) Department of Pathology, Asahikawa Medical College, 4-5-3-11, Nishikagura, Asahikawa, 078, Japan, JP |
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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.
Received: 22 August 1997 / Revised: 7 October 1997 |
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Keywords: | HLA Peptide VKH disease Tyrosinase T-cell response |
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