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Identification of autoantigens in Vogt-Koyanagi-Harada disease using recombinant retrovirus encoding melanocyte-specitic antigen genes

Research Project

Project/Area Number 12671722
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionKeio University

Principal Investigator

FUJITA Tomonobu  School of Medicine, Keio University, Instructor, 医学部, 助手 (20199334)

Co-Investigator(Kenkyū-buntansha) TAKEUCHI Masaru  Tokyo Medical University, Assistant Professor, 医学部, 講師 (40260939)
USUI Masahiko  Tokyo Medical University, Professor, 医学部, 教授 (40074570)
KAWAKAMI Yutaka  School of Medicine, Keio University, Professor, 医学部, 教授 (50161287)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsVokt-Koyanagi-Harada disease / Autoantigens / Melanocytes / T lymphocytes / HLA-DR / KU-MEL-1 / 原田病 / メラノサイト
Research Abstract

Vogt-Koyanagi-Harada disease (VKH) appears to be an autoimmune disease against melanocytes. Inflammatory nature of the uveitis and a significant association with HLA-DRB1*0405 suggest that CD4+ T cells reactive to melanocyte-specific proteins presented by HLA-DRB1*0405 are involved in the development of VKH. We have been identified many melanoma antigens recognized by tumor infiltrating T lymphocytes, including melanosomal antigen (tyrosinase, TRP1, TRP2, gp100, and MART1). In the immunotherapy for patients with melanoma, skin depigmentation sometimes occurs and correlates with melanoma regression, suggesting that these antigens are also involved in autoimmune responses to melanocytes. To identify VKH-specific autoantigens, we have analyzed T cell responses against melanocytes in VKH. T cells stimulated with melanocytes in choroid plexus may be enriched in cerebrospinal fluids. We initially attempted to generate some of T cell lines and clones from lymphocytes in cerebrospinal fluids of VKH patients. Total of 61 T cell clones were isolated from 3 VKH patients by the limiting dilution method. 24 clones from a patient recognized lysate from cultured melanoma cell line (Skmel23) in an HLA- DR restricted manner. Their responses against 293IMDR1 or 293CIITA co-transfected with HLA-DRB1*0405 and various melanocyte-specific antigen cDNAs were evaluated. KU-MEL-1 was recognized by one T cell line and one clone in HLA-DRB1*0405 restricted manner. Furthermore, IgG antibodies against KU-MEL-1 were detected in the sera from 15 of 26 (58%) VKH patients. Therefore KU-MEL-1 may be involved in development of VKH as one of the auto antigens recognized by CD4+ T cells. Identification of auto antigens recognized by T cells may lead to understanding of the pathological process involved in VKH as well as to development of new diagnostic and therapeutic methods for VKH patients.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Kawakami Y.Fujita T.et al.: "T cell responses to melanoma and melanocytes"Pigment Cell Research. 13. 166-169 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kiniwa Y, Fujita T., et al.: "Tumor Antigens Isolated from a Patient with Vitiligo and T-Cell-infiltrated Melanoma"Cancer Research. 61. 7900-7906 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Usui M.et al.: "Revised diagnostic criteria for Vogt-Koyanagi-Harada disease : report of an international committee on nomenclature"Am J Ophthalmol. 131・5. 647-652 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 河上 裕: "メラノーマと色素細胞に対するT細胞応答"組織培養工学. 26・10. 398-402 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 河上 裕: "メラノーマとメラノサイ卜に対する免疫応答の分子機構"日本皮膚科学会雑誌. 111・12. 1701-1703 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawakami Y. Y. Suzuki, T. Shofuda, Y. Kiniwa, T. Inozume, K. Dan T. Sakurai, and T. Fujita: "T cell responses to melanoma and melanocytes"Pigment Cell Research. 13 (Suppl 8). 166-169 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kiniwa Y, Fuiita T. Akada M, Ito K, Shofuda T, Suzuki Y, Yamamoto A, Saida T, Kawakami Y: "Tumor Antigens Isolated from a Patient with Vitiligo and T-Cell-infiltrated Melanoma"Cancer Research. 61. 7900-7906 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Read RW, Holland GN, Rao NA, Tabbara KF, Ohno S, Arellanes-Garcia L, Pivetti-Pezzi P, Tessler HH, Usui M: "Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature"Am. J. Ophthalmol. 131 (5). 647-652 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kiniwa Y, Fujita T, Kawakami Y: "Tumor Antigens Isolated from a Patient with Vitiligo and T-Cell-infiltrated Melanoma"Cancer Research. 61. 7900-7906 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawakami Y,Fujita T. et al.: "T cell immune responses against melanoma and melanocytes in cancer and autoimmunity"Pigment Cell Research. 13. 163-169 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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