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Peptide superagonists Establishment of their identification and it's application

Research Project

Project/Area Number 12557031
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Immunology
Research InstitutionSaitama Medical University (2001)
Kumamoto University (2000)

Principal Investigator

MATSUSHITA Sho  Saitama Medial School, Faculty of Medicine Professor and Chairman, 医学部, 教授 (50167649)

Co-Investigator(Kenkyū-buntansha) NAKASHIMA Toshihiro  Chemo-Sero-Therapeutic Research Institute, First Research Department, Senior Research Scientist, 第一研究部, 上級研究員
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordspeptide superagonists / combinatorial peptide library / CD4T cell clones / class II HLA / CD29 / interleukins / T-cell survival / limiting dilution / HLA class II分子 / random peptide / mimicry peptide / 自己免疫病 / T細胞 / ペプチド
Research Abstract

As far as peripheral T cells of unknown specificity are concerned, clones per se could hardly be obtained to render it difficult to propagate T cells, to a degree sufficient for testing. In order to overcome the difficulty, an attempt has been made to stimulate T cells with an immobilized anti-CD3 antibody in the presence of IL-2, but the long-term maintenance of T Cells could not readily achieve. This is supposedly due to lack of physiological response of APC via APC-peptide-T cell interaction. Thus, there is a need for developing a process for proliferating peripheral T cells of unknown specificity for cloning, as well as for effective analysis of epitopes recognized by said T cells
In the previous study, it was observed that some peptide partial agonists support T cell survival (Matsushita, S. et al. , J. Immunol. 1997, 158 : 5685-5691). It was also observed that an agonistic anti-CD29 antibody MAR4 increased the efficiency in establishing T cell clones from PBMC, both suppressing antigen-driven / activation-induced cell death and by enhancing the T cell proliferation, only in the presence of TCR/CD3-mediated stimulation (Tanaka, Y. et al. , Hum. Immunol. 1998, 59 : 343-351). Moreover, it was observed that culture supernatant of antigen-stimulated T cells in the presence of monocytes, increased the efficiency of cloning, when added to culture wells for limiting dilution
Under the circumstances, we constructed combinational randomized peptide library and stimulated peripheral blood- or tissue-derived T cells with this library in the presence of interleukins and agonistic anti-CD29, so that the T cell are proliferated and cloned. The isolated T cell clone is then analyzed for its epitope recognition to identify epitopes recognized by said clone by combinatorial assay with peptide library. Based on the identified peptide sequence, natural peptide ligands recognized by the isolated T cell clone can then be identified by pattern match search with database of sequence

Report

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

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Tabata, H.Matsuoka, T., Endo, F., Nishimura, Y., Matsushita, S.: "Ligation of HLA-DR molecules on B cells induces enhanced expression of IgM heavy chain genes in association with Syk activation"J. Boil. Chem.. 275. 34998-35005 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shigematsu, H., Shimoda, S., Nakamura, M., Matsushita, S., Nishimura, Y., Sakamoto, N., Ichiki, Y., Niho, Y., Gershwin, E., 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(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsuoka, T., Tabata, H., 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(和文)」より
    • Related Report
      2001 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, 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(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsushita, S., Tanaka, Y., Matsuoka, T., Nakashima, T.: "Clonal expansion of freshly isolated CD4T cells by randomized peptide and identification of peptide ligands using combinatorial peptide libraries"Eur. J. Immunol.. 31. 2395-2402 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohyama, H., Matsushita, S., Hatano, K., Kato, N., Nishimura, F., Takashiba, S., Murayama, Y.: "T cell responses to major membrane protein II (MMP II) of Mycobacterium Leprae are restricted by HLA-DR molecules in patients with leprosy"Vaccine. 20. 475-482 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 松下 祥 他: "コンパクト臨床アレルギー学"南江堂. 370 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ito H. Matsuhita S. Tokano Y. Nishimura H. Tanaka Y. Fujisao S. Mitsuya H. Hashimoto H. and Nishimura Y.: "Analysis of T-cell responses to the β 2-glycoprotein I-derived peptide library in patients with anti- β 2-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
      2001 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
      2001 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 ofr 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
      2001 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
      2001 Final Research Report Summary
  • [Publications] Oyaizu K, Ohyama H., Nishimura F, Kurihara H, Matsushita S, Maeda H, Kokeguchi S, Hongyo H, Takashiba S, and Murayama Y: "Identification and characterization of B-cell eptopes of a 53-kDa outer membrance protein from Porphyromonas gingivalis"Oral Microbiol Immunol. 16. 73-78 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 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, Ohsima K and Izuhara K: "Localization of human interleukin-13 receptor in non-hematopietic cells"Cytokine. 13. 75-84 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Minohara M, Ochi H, Matsuhita 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. 57. 447-456 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inoue R, Matsuhita 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. 31. 1126-1134 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsushita S, Tanaka Y, Matsuoka T and Nakashima T: "Clonal expansion fo freshly isolated CD4T cells by randomized peptides and identification of peptide ligands using combinatorial peptide libraries"Eur. J. Immunol. 31. 2395-2402 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohyama H, Matsuhita S, Hatano K, Kato N, Nishimura F, Takashiba S and Murayama Y: "T cell responses to major membrane protein II (MMP II) of Mycobacterium Leprae are restricted by HLA-DR molecules in patients with leprosy"Vaccine. 20. 475-482 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kudo H, Matsuoka T, Mitsuya H, Nishimura Y and Matsuhita S: "Cross-linking HLA-DR molecules on Th1 cells induces anergy in association with increased level of cyclin-dependent kinase inhibitor p27Kip1"Immunol. Lett. 81. 149-155 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tabata, H., Matsuoka, T., Endo, F., Nishimura, Y., 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)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shigematsu, H., Shimoda, S., Nakamura, M., Matsushita, S., Nishimura, Y., Sakamoto, N., Ichiki, Y., Niho, Y., Gershwin, E., 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)

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

    • Related Report
      2001 Annual Research Report
  • [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., Izuhara, K.: "Localization of human interleukin-13 receptor in non-hematopoietic cells"Cytokine. 13. 75-84 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsushita, S., Tanaka, Y., Matsuoka, T., Nakashima, T.: "Clonal expansion of freshly isolated CD4T cells by randomized peptide and identification of peptide ligands using combinatorial peptide libraries"Eur. J. Immunol.. 31. 2395-2402 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohyama, H., Matsushita, S., Hatano, K., Kato, N., Nishimura, F., Takashiba, S., Murayama, Y.: "T cell responses to major membrane protein II (MMP II) of Mycobacterium Leprae are restricted by HLA-DR molecules in patients with leprosy"Vaccine. 20. 475-482 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 松下 祥 他: "コンパクト臨床アレルギー学"南江堂. 370 (2000)

    • Related Report
      2001 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] Akaiwa,M., et al.: "Localization of human interleukin-13 receptor in non-hematopoietic cells."Cytokine. 13. 75-84 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Minohara,M., et al.: "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)). (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

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Published: 2001-04-01   Modified: 2016-04-21  

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