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Immune regulation mediated by signaling through HLA molecules

Research Project

Project/Area Number 09670340
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・School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (50167649)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsHAL / Major histocompatibility complex / class II / DR / DQ / DP / immune response genes / antigen-presenting cells / signal transduction / peptide antigens / DA / class II HLA / monocyte / モノカイン / T細胞
Research Abstract

The class II HLA molecule (HLA-DR, -DQ or -DP) is expressed on various antigen presenting cells (APC), B cells and activated T cells in humans. Proteolytic fragments of peptides processed by APC that match thc physicochemical character of the peptide-binding grooves formed by alpha and beta chains of class II HLA molecules are expressed on the surface of APC to be recognized by T cells. The highly polymorphic amino acid residues of the class II HLA molecules reside within the grooves, indicating that genetic polymorphism accounts for the wide spectrum of peptides capable of binding. Side chains of an HLA-DR1-binding peptide project from the peptide backbone approximately every 130゚C within the groove. Many DR-binding peptide motifs reported to date follow the 9-mer peptide pattern AxxBxCDxE, with A, B, C, D, and E residues functioning for binding to HLA, thereby designated as "anchors". On the contrary, the x residues are recognized by T cells through T-cell receptor (TCR). Analogue peptides with single residue substitutions at x residues changed signals in T cells, leading to quantitative (TCR antagonism, etc.) and qualitative (anergy/survival, etc.) changes in human T-cell clonal responses. Certain analogues changed signals in monocytes, leading to the up-regulation of IL-12. Furthermore, cross-linking of class II HLA molecules on monocytes using mAbs lead to up-regulation of monokines, in which HLA-DR, -DQ, and -DP play differential roles. Thus, HLA molecules when recognized by TCR, not only present peptide antigens to T cells but also transmit signals to APC, where the polymorphism and heterogeneity of HLA molecules play important roles.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Matsushita, S., et al.: "Evidence for self-and non-self-peptide partial agonists that prolong clonal survival of mature T cells in vitro." J. Immunol.158. 5685-5691 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsushita, S., et al.: "Partial activation of human T cells by peptide analogs on live APC: induction of clonal anergy associated with protein tyrosine dephosphorylation." Hum. Immunol.53. 73-80 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujita, H., et al.: "Evidence for human CD4^+ T cell clones specific to p53 cryptic self peptides and responding to p53 proteins of both wild and mutant forms." Eur. J. Immunol.28. 305-316 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, Y., et al.: "Efficient induction of human CD4^+ T cell lines reactive with a self-K-ras-derived peptide in vitro, using a mAb to CD29." Hum. Immunol.59. 343-351 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohyama, H., et al.: "T cell responses to 53-kDa outer membrane protein of Porphyromonas gingivalis in humans with early-onset periodontitis." Hum. Immunol.59. 635-643 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 松下 祥: "MHC・ペプチド複合体と抗原提示" 宮坂昌之, 谷口克編:「標準免疫学」, 医学書院, (東京), 17 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 松下 祥, 他: "免疫の遺伝" 今村 孝編:「21世紀への遺伝学V. 人類遺伝学」, 裳華房, (東京), 30 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsushita, S., Kohsaka, H.and Nishimura, Y.: "Evidence for self-and non-self-peptide partial agonists that prolong clonal survival of mature T cells in vitro." J.Immunol.158. 5685-5691 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kanai, T., Nomura, Y., Segawa, M., Takagi, K., Senju, S., Matsushita, S.and Nishimura, Y.: "Immuno-suppressive peptides for a human T cell clone autoreactive to a unique acetylcholine receptor alpha subunit peptide presented by the disease susceptible HLA-DQ6 in infant-onset Myasthenia Gravis." Hum.Immunol.56. 28-38 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yokomizo, H., Matsushita, S., Murakami, S., Fujita, H., Shirouzu, M., Yokoyama, S., Ogawa, M.and Nishimura, Y.: "Augmentation of immune response by an analog of the antigenic peptide in a human T-cell clone recognizing mutated Ras-derived peptides." Hum.Immunol.52. 22-32 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujisao, S., Nishimura, Y.and Matsushita, S.: "Evaluation of peptide-HLA binding by an enzyme-linked assay and its application to the detailed peptide motifs for HLA-DR9 (DRB1^*0901)." J.Immunol.Methods. 201. 157-163 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oiso, M., Nishi T., Nishimura, Y.and Matsushita, S.: "Differential peptide binding to HLA-DQ8 and DQ9 differing only at DQbeta^<57>." Hum.Immunol.52. 47-53 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsushita, S.and Nishimura Y.: "Partial activation of human T cells by peptide analogs on live APC : induction of clonal anergy associated with protein tyrosine dephosphorylation." Hum.Immunol.53. 73-80 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujita , H., Senju, S., Yokomizo, H., Saya, H., Ogawa, M., Matsushita, S.and Nishimura, Y.: "Evidence for human CD4+ T cell clones specific to p53 crytic self peptides and responding to p53 proteins of both wild and mutant forms." Eur.J.Immunol.28. 305-316 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oiso, M., Matsushita, S., Nishi, T., Ishikawa, T., Nakano, N., Yoshida, K., Kikutani, H.and Nishimura, Y.: "Differential binding of peptides substituted at a putative C-terminal anchor residue to I-Ag^7beta56Hisbeta57Ser and I-Ag^7beta56Probeta57Asp." Immunogenetics. 47. 411-414 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, Y., Ogawa, M., Nishimura, Y.and Matsushita, S.: "Efficient induction of human CD4+ T cell lines reactive with a self-K-ras-derived peptide in vitro, using a mAb to CD29." Hum.Immunol.59. 343-351 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohyama, H., Matsushita, S., Kato, N., Nishimura, F., Oyaizu, K., Kokeguchi, S., Kurihara, H., Takashiba, S., Nishimura, Y.and Murayama, Y.: "T cell responses to 53-kDa outer membrane protein of Porphyromonas gingivalis in humans with early-onset periodontitis." Hum.Immunol.59. 635-643 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 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
      1998 Final Research Report Summary
  • [Publications] Matsushita,S et al.: "Evidence for self-and non-self-peptide partial agonists that prolong clonal survival of mature T cells in vitro" J.Immunol.158. 5685-5691 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsushita.S et al.: "Partial activation of human T cells by peptide analogs on live APC:induction of clonal anergy associated with protein tyrosine dephosphorylation." Hum.Immunol.53. 73-80 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fujita,H et al.: "Evidence for human CD4^+ T cell clones spesific to p53 cryptic self peptides and responding to p53 proteins of both wild and mutant forms." Eur.J.Immunol.28. 305-316 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka,Y et al.: "Effection induction of human CD4^+ T cell lines rwactive with a self-K-ras-derived peptide in vitro,using a mAb to CD29." Hum.Immunol.59. 343-351 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohyama,H et al.: "T cell responses to 53-kDa outer membrane protein of Porphyromonas gingivalis in humans with early-onset periodontitis." Hum.Immunol.59. 635-643 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsushita,S et al.: "Peptid 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
      1998 Annual Research Report
  • [Publications] 松下祥: "MHC・ペプチド複合体と抗原提示" 宮坂昌之、谷口克編:「標準免疫縛」,医学書院(東京), 17 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 松下祥、他: "免疫の遺伝" 今村 孝編:「21世紀への遺伝学V.人類遺伝学」裳華房(東京), 30 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oiso, M. et al.: "Differential binding of peptides substituted at a putative C-terminal anchor residue to I-Ag7 β57Ser and I-Ag7 β56Proβ57Asp" Immunogenetics. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujita, H. et al.: "Evidence for human CD4_+ T Cell clones specific to p53 cryptic self peptides and respinding to p53 proteins of both wild and mutant forms" Eur. J. Immunol.28. 305-316 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsushita, S. et al.: "Evidence for self-and non-self-peptide partial agonists that prolong clonal survival of mature T cells in vitro" J. Immunol.158. 5685-5691 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yokomizo, H. et al.: "Augmentation of immune response by an analog of the antigenic peptide in a human T-cell clone recognizing mutated Ras-derived peptides" Hum. Immunol.52. 22-32 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Oiso, M. et al.: "Differential peptide binding to HLA-DQ8 and DQ9 differing only at DQ β57" Hum. Immunol.52. 47-53 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsushita, S. et al.: "Partial activation of human T cells by peptide analogs on live APC : induction of clonal anergy associated with protein tyrosine dephosphorylation" Hum. Immunol.53. 73-80 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsushita, S. et al.: "Molecular and genetic approaches to diseases" HLA-peptide complex and diseases (in press),

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka, Y. et al.: "Leukocyte Typing VI" Effect of mAbs to T-cell and adhesion structures on a proliferative response of a CD4+ T cell clone with a paracrine growth property, 111 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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