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Analyses of immunological molecular mimicry in T-cell antigen recognition

Research Project

Project/Area Number 11670327
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKumamoto University

Principal Investigator

MATSUSHITA Sho  Kumamoto University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究科, 助教授 (50167649)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,800,000 (Direct Cost: ¥2,800,000)
Keywordspeptides / superagonists / molecular mimicry / T cells / mass spectrometry / high throughput screening / combinatorial chemistry / conbinatorial peptide library
Research Abstract

While the recognition of peptide antigens by T cells via the TCR has exquisite specificity, many studies have shown flexibility in such recognition. Even certain peptides minimally homologous with a wild-type peptide, exhibit stronger proliferation-inducing activity than did a wild-type on relevant T cells, thereby designated peptide superagonists. We synthesized a set of X9 combinatorial peptide libraries with flanking residues of the core sequence recognized by a K-ras-reactive CD4+ T cell clone. Based on the results for each position of the antigenic peptide, we synthesized several artificial peptides and tested their potential to induce proliferation of the T cell clone. Unexpectedly, none of such peptides induced stronger proliferative responses than did the wild-type. We then used mass spectrometry to overcome drawbacks, and we identified two peptide species that exhibit markedly potent stimulation, as compared with the wild-type.
T cells of unknown specificity are not readily cloned nor are they expanded in sufficient numbers, for full-scale analyses. To overcome these drawbacks, we synthesized Xn (n=9-19) peptides consisting of 9 to 19 residues with random sequences, and found that X19 is effective for the propagation of single CD4T cells, when IL-4, IL-7, IL-9, IL-15 and agonistic Ab to CD29 were included in the culture. Use of combinatorial peptide libraries and pattern-match search on a T cell clone resulted in peptide ligand candidates, one of which induced proliferation, as did protein molecules carrying the corresponding sequence. These strategies combined will contribute to the identification of mimicry peptides, for T cells in autoimmunity.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Matsushita,S., et al.: "Peptide length-dependent TCR antagonism on class II HLA-restricted responses of PBMC and T-cell clones."Eur.J.Immunol.. 29. 431-436 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka,Y., et al.: "Identification of peptide superagonists for a self-K-ras-reactive CD4+ T cell clone by use of combinatorial peptide libraries and mass spectrometry."J.Immunol.. 162. 7155-7161 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito,H., et al.: "Analysis of T-cell responses to the β2-glycoprotein I-derived peptide library in patients with anti-β2-glycoprotein I antibody-associated autoimmunity."Hum.Immunol.. 61. 366-377 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tabata,H., et al.: "Ligation of HLA-DR molecules on B cells induces enhanced expression of IgM heavy chain genes in association with Syk activation."J.Biol.Chem.. 275. 34998-35005 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigematsu,H., et al.: "Fine specificity of T cells reactive to human PDC-E2 163-176 peptide, the immunodominant autoantigen in primary biliary cirrhosis : Implications for"Hepatology. 32. 901-909 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuoka,T., et al.: "Monocytes are differentially activated through HLA-DR, -DQ and -DP molecules via mitogen-activated protein kinases."J.Immunol.. 166. 2202-2208 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 松下祥: "コンパクト臨床アレルギー学"南光堂. 9 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 松下祥: "アレルギーナビゲーター"メディカルレビュー社(印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsushita, S., and Matsuoka, T.: "Peptide length-dependent TCR antagonism on class II HLA-restricted responses of PBMC and T-cell clones."Eur.J.Immunol.. 29. 431-436 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yun, C., Senju, S., Fujita, H., Tsuji, Y., Irie, A., Matsushita, S.and Nishimura, Y.: "Augmentation of immune response by altered peptide ligands of the antigenic peptide in a human CD4+ T cell clone reacting to TEL/AML1 fusion protein."Tissue Antigens. 54. 153-161 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka, Y., Ohyama, H., Ogawa, M., Nishimura, Y.and Matsushita, S.: "Identification of peptide superagonists for a self-K-ras-reactive CD4+ T cell clone by use of combinatorial peptide libraries and mass spectrometry."J.Immunol.. 162. 7155-7161 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito, H., Matsushita, S., Tokano, Y., Nishimura, H., Tanaka, Y., Fujisao, S., Mitsuya, H., Hashimoto, H.and Nishimura, Y.: "Analysis of T-cell responses to the β2-glycoprotein I-derived peptide library in patients with anti-β2-glycoprotein I antibody-associated autoimmunity."Hum.Immunol.. 61. 366-377 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tabata, H., Matsuoka, T., Endo, F., Nishimura, Y.and Matsushita, S.: "Ligation of HLA-DR molecules on B cells induces enhanced expression of IgM heavy chain genes in association with Syk activation."J.Biol.Chem.. 275. 34998-35005 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigematsu, H., Shimoda, S., Nakamura, M., Matsushita, S., Nishimura, Y., Sakamoto, N., Ichiki, Y., Niho, Y., Gershwin, E.and Ishibashi, H.: "Fine specificity of T cells reactive to human PDC-E2 163-176 peptide, the immunodominant autoantigen in primary biliary cirrhosis : Implications for molecular mimicry and cross-recognition among mitochondrial autoantigens."Hepatology. 32. 901-909 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuoka, T., Tabata, H.and Matsushita, S.: "Monocytes are differentially activated through HLA-DR,-DQ and -DP molecules via mitogen-activated protein kinases."J.Immunol.. 166. 2202-2208 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akaiwa, M., Yu, B., Umeshita, R., Terada, N., Suto, H., Koga, T., Arima, K., Matsushita, S., Saito, H., Ogawa, H., Furue, M., Hamasaki, N., Ohshima, K.and Izuhara, K.: "Localization of human interleukin-13 receptor in non-hematopoietic cells."Cytokine. 13. 75-84 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Minohara, M., Ochi, H., Matsushita, S., Irie, A., Nishimura, Y.and Kira, J-I.: "Differences between T cell reactivities to major myelin protein-derived peptides in opticospinal and conventional forms of multiple sclerosis and healthy controls."Tissue Antigens. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inoue, R., Matsushita, S., Kaneko, H., Shinoda, S., Ito, R., Nishimura, Y.and Kondo, N.: "Identification of β-lactoglobulin-derived peptides and class II HLA molecules recognized by T Cells from the patients with milk allergy."Clin.Exp.Allergy. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsushita,S., et al.: "Peptide length-dependent TCR antagonism on class II HLA-restricted responses of PBMC and T-cell clones."Eur.J.Immunol.. 29. 431-436 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanaka,Y., et al.: "Identification of peptide superagonists for a self-K-ras-reactive CD4+ T cell clone by use of combinatorial peptide libraries and mass spectrometry."J.Immunol.. 162. 7155-7161 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ito,H., et al.: "Analysis of T-cell responses to the β2-glycoprotein I-derived peptide library in patients with anti-β2-glycoprotein I antibody-associated autoimmunity."Hum.Immunol.. 61. 366-377 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tabata,H., et al.: "Ligation of HLA-DR molecules on B cells induces enhanced expression of IgM heavy chain genes in association with Syk activation."J.Biol.Chem.. 275. 34998-35005 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigematsu,H., et al.: "Fine specificity of T cells reactive to human PDC-E2 163-176 peptide, the immunodominant autoantigen in primary biliary cirrhosis : Implications for"Hepatology. 32. 901-909 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsuoka,T., et al.: "Monocytes are differentially activated through HLA-DR, -DQ and -DP molecules via mitogen-activated protein kinases."J.Immunol.. 166. 2202-2208 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 松下祥: "コンパクト臨床アレルギー学"南光堂. 9 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 松下祥: "アレルギーナビゲーター"メディカルレビュー社(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sho Matsushita,et al.: "Peptide length-dependent TCR antagonism on class II HLA-restricted responses of peripheral blood mononuclear cells and T cell clones."European Journal of Immunology. 29. 431-436 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takako Matsuoka,et al.: "Ligation of HLA-DR,-DQ and -DP molecules on monocytes differentially activates IL-1β,IL-6,IL-10,IL-12,TNF-α and GM-CSF secretion."FASEB Journal. 13. A275 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroki Tabata,et al.: "Immune regulation mediated by class II HLA molecules on B cells."FASEB Journal. 13. A275 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sho Matsushita,et al.: "Short peptides exhibit TCR antagonism on claass II HLA-restricted responses of PBMC and T-cell clones."FASEB Journal. 13. A276 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yun,C.,et al.: "Augmentation of immune response by altered peptide ligands of the antigenic peptide in a human CD4^+ T cell clone reacting to TEL/AML1 fusion protein."Tissue Antigens. 54. 153-161 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshihiko Tanaka,et al.: "Identification of peptide superagonists for a self-K-ras-reactive CD4^+ T cell clone using combinatorial peptide libraries and mass spectrometry."Journal of Immunology. 162. 7155-7161 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 松下 祥、他: "コンパクト臨床アレルギー学"南光堂(印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] 松下 祥、他: "アレルギーナビゲーター"メディカルレビュー社(印刷中).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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