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IMMUNE FUNCTION OF NONCLASSICAL MHC CLASS I MOLECULE

Research Project

Project/Area Number 07457090
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionAichi Cancer Center

Principal Investigator

OBATA Yuichi  AICHI CANCER CENTER,LAB.OF IMMUNOLOGY,SECTION HEAD, 免疫学部, 室長 (30177290)

Co-Investigator(Kenkyū-buntansha) DOI Satoru  AICHI CANCER CENTER,LAB.OF IMMUNOLOGY,SENIOR RESEARCHER, 免疫学部, 主任研究員 (60227684)
TAKAHASHI Toshitada  AICHI CANCER CENTER,VICE DIRECTOR, 副所長 (00124529)
TSUJIMURA Kunio  AICHI CANCER CENTER,LAB.OF IMMUNOLOGY,SENIOR RESEARCHER, 免疫学部, 主任研究員 (10227407)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥3,600,000 (Direct Cost: ¥3,600,000)
KeywordsImmune system / Mouse TL molecule / Nonclassical MHC class I moleculesceramic coating / gammadelta T cells / Positive selection / alphabeta T cells / Transgenic mouse / Antigen / γδT細胞 / マウスTL抗原 / 非古典的MHCクラスI抗原 / 抗原ペプチド / TCR / 遺伝子欠失マウス
Research Abstract

To understand the role of nonclassical MHC class I molecules in the immune system, we have studied mouse TL molecules, a prototype of nonclassical MHC class I mosecules. The specific aims of this study are (a) elucidation of function of TL in T-cell differentiation, (b) identification of TL-binding molecules and (c) delineation of mechanisms for T-cell recognition of TL moleculed and for cytotoxic acitivity against TL^+ cells. The following results have been obtained :
1. Positive selection of gammadelta T-cells by TL expressed on thymocytes. Two transgenic mouse strains expressing a large amount of Tla^a-3-TL molecules have been derived on C3H background (No TL strains expression on thymocytes). One strain shows abnormal thymic develpment and the deviation of T-cell defferentiation toward the gammadelta lineage. The other strain does not show any obvious abnormalities, but gammadelta CTL was specifically induced in this strain, upon the induction of CTL recognizing TL.These results ind … More icated conclusively that TL expressed on thymocytes engages in the positive selection of gammadelta T cells.
2. Identification of TL-binding mosecules. TL molecule was first isolated from TL^+ cells using TL-affinity columns. Molecules complexed with TL were then analyzed by Reverse-phase HPLC,an automated amino acid sequencer, and a tandem mass spectrometry. As a control experment, we isolated H-2K^b-binding peptides and determined their individual sequences and the binding motives. Although we isolated TL molecule amount similar to H-2K^b, the identification of TL-binding mosecules have been very difficult. Thus, the results suggested possibilities that (1) N-termini of TL-binding peptides are modified and blocked, (2) non-peptides such as lipids are binding, or (3) no molecules bind to TL.We are now testing these possibilities.
3. Cellular mechanism of CTL acitivity and invovment of CD4 T cells. (a) cytotoxic mechanism of anti-TL CTL.The majority of CTL against RL are alphabeta T-cells although some gammadelta CTL are induced in TL-transgenic mice. In the analysis of alphabeta CTL,they are found to be divided into two groups according to their cytotoxic acitivity against various TL^+ target cells. Type I CTL kills all TL^+ cells regardless of their orgins, while Type II CTL kills only Fas^+TL^+ spleen cells of Tg. Con.3-1 transgenic mouse. Type I CTL mediates its cytotoxicity by perforin/granzyme, while Type II CTL by FasL.The difference of cytotoxic mechanisms among CTL may be resulted from the differnce in the affinity between TL and TCR or from the difference in TL-binding molecules. (b) Involvement of CD4 T cells. CD4 T cells are required for the rcognition of TL as a transplantation rejectio antigen and for the generation of CTL against requires, although TL is a member of MHC class I antigen family. The results indicate that the helper function of CD4 T cells is required for full activation of CD8 effector cells, because the precursor frequency of CD8^+ recognizing TL is too low to mediate skin graft rejection or to induce CTL. Less

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Tsuji, K.: "Requirement of CD4T cells for skin graft rejection against thymus leukemia(TL)antigen and muliple epitopes on the TL molecule recognized by CD4 T cells." J.immunol.159. 159-166 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsujimura, K.: "Two types of anti-TL CTL clones with distinct target specificty:differences in cytotoxic mechanisma and accessory molecule requirement." J.Immunol.160(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takeuchi, M.: "Suppression of spontaneous uveoretinitis development by non-immunopathogenic peptide immunization." Eur.J.Immunol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Doi, T.S.: "NA-κB RelA-deficient lymphocytes:Nomal development of T cells and B cells,impaired production of IgA and IgG1 and reduced proliferative responses." J.Exp.Med.185. 953-961 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 辻村 邦夫: "γδ型T細胞への抗原定分子" Annual Reviw免疫1997. 174-182 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 土井 貴裕(了): "NF-κBファミリーによるリンパ球分化と機能の調節" 細胞工学. 17. 57-64 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 高橋 利忠(他): "シンプル免疫学" 南光堂, 221 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshikawa, K., Seto, M., Ueda, R., Obata, Y., Aoki, S.and Takahashi, T.: "Molecular cloning of the gene coding for the murine T-cell antigen CD7" Immunogenetics. 41. 159-161 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsujimura, K., Takahashi, T., Morita, A., Nishiwaki, H., Iwase, S.and Obata, Y.: "Positive selection of gammadelta CTL by TL antigen expressed in the thymus" J.Exp.Med.184. 2175-2184 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Chen, B.-G., Wada, H., Matsutake, T., Uenaka, A., Obata, Y.and Nakayama, E: "Inhibition by CsA and FK506 of the in vtro proliferative response of gammadelta T cell on stimulation with and TCRdelta monoclonal antibody." Transplant.Immunol. 4. 158-162 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Okamoto, S., Yoshikawa, K., Obata, Y., Shibuya, M., Aoki, A., Yoshida, J.and Takahashi, T.: "Monoclonal antibody against the fusion junction of a deletion-mutant epidermal growth factor receptor" Brit.J.Cancer. 73. 1366-1372 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Taguchi, O., Takahashi, T.: "Administration of anti-interleukin-2 receptor alpha antibody in vivo induces localized autoimmune disease." Eur.J.Immunol.26. 1608-1612 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Taguchi, O., Takahashi, T.: "Mouse models of autoimmune disease suggest that self-tolerance is maintained by unresponsive autoreactive T cells" Immunology. 89. 13-19 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sekimata, M., Tsujimura, K., Tanaka, J., Takeuchi, Y., Inagaki, N and Inagaki, M.: "Detection of protein kinase activity specifically activated at metaphase transition." J.Cell Biol.132. 635-642 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Doi, T.S.Takahashi, T., Taguchi, O., Azuma, T.and Obata, Y.: "NF-_<kappa>B RelA-deficient lymphocytes : Normal development of T cells and B cells, impaired producion of IgA and IgG1 and reduced" J.Exp.Med.185. 953-961 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuji, K., Obata, Y., Takahashi, T.Arata, J.and Nakayama, E.: "Requirement of CD4 T cells for skin graft rejection against thymus leukemia (TL) antigen and multiple epitopes on the TL molecule recognized by CD4 cells." J.Immunol.159. 159-166 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsujimura, K., Takahashi, T.Iwase, S., Matsudaira, Y., Kaneko, Y., Yagita, H.and Obata, Y.: "Two types of anti-TL CTL clones with distinct target specificity : differences in cytotoxic mechanisms and accessory molecule requirement" J.Immunol.160 (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takeuchi, M., Kezuka, T., Inoue, H., Sakai, J., Usui, M., Takahashi, T.and Taguchi, O.: "Suppression of spontaneous uveoretinitis development by non-immunopathogenic peptide immunization" Eur.J.Immunol.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuji,K.: "Requirement of CD4 T cells for skin graft rejection against thymus leukemia(TL) antigen and multiple epitopes on the TL molecule recognized by CD4 T cells." J.Immunol.159. 159-166 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsujimura,K.: "Two types of anti-TL CTL clones with distinct target specificty: differences in cytotoxic mechanisms and accessory molecule requirement." J.Immunol.160(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takeuchi,M.: "Suppression of spontaneous uveoretinitis development by non-immunopathogenic peptide immunization." Eur.J.Immunol.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Doi,T.S.: "NF-χB RelA-deficient lymphocytes: Normal development of T cells and B cells,impaired production of IgA and lgGl and reduced proliferative responses." J.Exp.Med.185. 953-961 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 辻村邦夫: "γδ細胞T細胞への抗原提示分子" Annual Review免疫1997. 174-182 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 土井貴裕(了): "NF-χBファミリーによるリンパ球分化と機能の調節" 細胞工学. 17. 57-64 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 高橋利忠(他): "シンプル免疫学" 南光堂, 221 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Chen,B.-G.: "Inhibition by CsA and FK506 of the in vitro proliferative response of γδ T cells on stimulation with anti-TCR δ monoclonal antibody." Transplant Immunol.4. 158-162 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okamoto,S.: "Monoclonal antibody against the fusion junction of a deletion-mutant epidermal growth factor receptor." Brit.J.Cancer. 73. 1366-1372 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsujimura,K.: "Positive selection of γδ CTL by TL antigen expressed in the thymus." J.Exp.Med.184. 2175-2184 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Doi,T.S.: "NF-κB RelA deficient lymphocytes : Normal development of T-cells and B-cells,impaired production of IgA and IgG1 and reduced proliferative responses." J.Exp.Med.185. 953-961 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshikawa, K.: "Molecular cloning of the gene coding for the murine T-cell antigen CD7." Immunogenetics. 41. 159-161 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Okamoto, S.: "Monoclonal antibody against the fusion junction of a deletion-mutant epidermal growth factor receptor." Brit. J. Cancer.in press.

    • Related Report
      1995 Annual Research Report
  • [Publications] 小幡 裕一: "TL遺伝子導入による細胞分化異常とリンパ腫発生" 蛋白質核酸酵素臨時増刊号「トランスジェニック動物」. 40. 2054-2061 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 小幡 裕一: "マウスTL分子とMHCクラスIb分子による抗原提示" Molecular Medicine臨時増刊号「免疫1995-96」. 32. 190-199 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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