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Development of HLA bound peptitides which have supressive activity.

Research Project

Project/Area Number 04557027
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

SASAZUKI Takehiko  Kyushu University, Medical Institute of Bioregulation, Department of Genetics, Professor, 生体防御医学研究所, 教授 (50014121)

Co-Investigator(Kenkyū-buntansha) KAMIKAWAJI Nobuhiro  Kyushu University, Medical Institute of Bioregulation, Department of Genetics, A, 生体防御医学研究所, 助手 (90224659)
KIMURA Akinori  Kyushu University, Medical Institute of Bioregulation, Department of Genetics, A, 生体防御医学研究所, 助教授 (60161551)
福井 宣規  九州大学, 生体防御医学研究所, 助手 (60243961)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥18,900,000 (Direct Cost: ¥18,900,000)
Fiscal Year 1994: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1993: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1992: ¥7,900,000 (Direct Cost: ¥7,900,000)
KeywordsHLA / Antigenic peptide / Immune response / Transgenic mouse / Genetic polymorphism / DNA typing / MHC / MHC結合性ペプチド / HLA-DP9 / トランスフェクタント
Research Abstract

There are many diseases caused by abnormal immune responses. To develop the non stimulatory peptide analog that binds to HLA molecule, we investigated the HLA-peptide interactions. Interaction of HLA-DP9 (DPA1*0201/DPB1*0901) molecule and M protein of serotype 12 (SS95/12) streptococcus has been investigated. Seven antigenic peptides restricted by the HLA-DP9 molecule were identified. Comparison of the amino acid sequences among these peptides revealed HLA-DP9-specific binding motif, which differs from the binding motif to the HLA-DR molecules. In an analysis of T cell responses to synthetic peptides in mice transgenic for HLA-DR51 and -DQ6, we found that DR51 and DQ6 transgenic mice acquired significant T cell response to the peptides. This indicated that HLA transgenic mouse should be a useful tool to examine the function of HLA molecules in vivo. We also developed the DNA typing method using PCR/SSOP analysis for HLA-A,HLA-DR,DQ and DP alleles, and found several new alleles. Using this method we determined several susceptible genes for autoimmune disease.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Rae SM Yeung, et al: "Human CD4-major histocompatibility comlex classII (DQW6) transgenic mice in an endogenous CD4/CD8-deficient background;Reconstitution of phenotype and human restricted function." J. Exp. Med.180. 1911-1920 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Wan XL, et al: "HLA-A and DRB4 genes in controlling the susceptibility to Hashimoto's Thyroiditis." Hum. Immunol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshizumi H,et al: "Generation of CD8_+ cytotoxic T lymphocytes that shows soluble factor-dependent lysis of autologous antigen presenting cells." Eur. J. Immunol.23. 3173-3180 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tamai H, et al: "Resistance to autoimmune thyroid disease is associated to HLA-DQ." J. Clin. Endocrinol.Metab.78. 94-97 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshida M, et al: "DNA typing of HLA-B gene in Takayasu's arteritis." Tissue Antigens.42. 87-90 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Dong RP, et al: "Difference in HLA-linked genetic background between mixed connective tissue disease and systemic lupus erythematosus." Tissue Antigens.41. 20-25 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Rae SM Yeung, et al.: "Human CD4-major histocompatibility complex class II (DQW6) transgenic mice in an endogenos CD4/CD8-deficient background : Reconstitution of phenotype and human restricted function." J.Exp.Med.180. 1911-1920 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Wan XL,et al.: "HLA-A and DRB4 genes in controlling the susceptibility to Hashimoto's Throiditis." Hum, Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshizumi H,et al.: "Generation of CD8+ aytotoxic T lymphocytes that shows soluble factor-dependent lysis of autologous antigen presenting cells." Eur.J.Immunol.23. 3173-3180 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tamai H,et al.: "Resistance to autoimmune thyroid disease is associated to HLA-DQ." J.Clin.Endocrinol.Metab. 78. 94-97 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshida M,et al.: "DNA typing of HLA-B gene in Takayasu's asteritis." Tissue Antigens.42. 87-90 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Dong RP,et al.: "Difference in HLA linked genetic background between mixed connective tissue disease and systemic lupus erythematosus。" Tissue Antigens.41. 20-25 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Dong RP.: "Characterization of T cell epitopes restricted by HLA-DP9 in streptococcal M12 protein." J. Immunol.(in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Wan XL.: "HLA-A and DRB4 genes in controlling the susceptibility to Hashimoto's Thyroiditis." Hum.Immunol.(in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Rae SM. Yeung: "Human CD4-major histocompatibility complex class II(DQW6)transqenic mice and endogenous CD4/CD8-deficient background:Reconstitution of phenotypeand human restricted function." J.Exp. Med.180. 1911-1920 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yamamoto K.: "Functional interaction between human histocompatibility leukocyte antigen(HLA)class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DO transgenic mice." J.Exp. Med.180. 165-171 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Satoh M.: "Genetic and immunological differences between Japanese patients with diffuse scleroderma and limited scleroderma." J. Rheumatol.21. 111-114 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Honda K: "Immunogenetic analysis of silicosis in Japan" Am.J.Resp.Cell Mol.Biol.8. 106-111 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Fukui Y: "Restricted expression of transgenic HLA-DRA gene in thymic epithelial cells and its role in aguisition of T cell tolerance to self-superantigens and processed DRalpha-derived peptide" Eur.J.Immunol.23. 1678-1686 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tamai H: "Resistance to autoimmune thyroid disease is associated with HLA-DQ" J.Clin.Endocrinol.Metab.78. 94-97 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Esaki Y: "Role of human major histocompatibility complex DQ molecules in superantigenicity of Streptococcus-derived protein" Infect.Immun.62. 1228-1235 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kimura A.: "DNA typing of HLA class II genes in B-lymphoblastoid cell lines homozygous for HLA" Tissue Antigens. 40. 5-12 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Fukui Y: "T cell repertoire in a transgenic C57BL/6 mice expressing the HLA-DRA gene on the X Chromosome" Immunogenetics. 37. 204-211 (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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