Molecular mechanisms of immune regulation.

1996 Fiscal Year Final Research Report Summary

• Project/Area Number: 05272104
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Research Institution: Kyushu University
• Principal Investigator: SASAZUKI Takehiko Medical Institute of Bioregulation, Kyushu University, Professor, 生体防御医学研究所, 教授 (50014121)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAI Yasunobu School of Medicine, Nagoya University, Professor, 医学部, 教授 (90158402) ; ARAI Ken-ichi The Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (00012782) ; TANIGUCHI Masaru School of Medicine, Chiba University, Professor, 医学部, 教授 (80110310) ; INOKO Hidetoshi School of Medicine, Tokai University, Professor, 医学部, 教授 (10101932) ; KATAGIRI Makoto School of Medicine, Asahikawa Medical College, Professor, 医学部, 教授 (10041823)
• Project Period (FY): 1993 – 1995
• Keywords: HLA / antigenic peptide / TCR / prosessing / proteosome

Research Abstract

To elucidate the molecular mechanisms of immune regulation in immune response to natural antigens in individuals, we investigated the recognition of HLA/peptide complexes by TCRs and the resultant cytokine expressions induced by interaction with the TCR.
1.We elucidated the immune regulation by HLA-class I and Class II molecules by examining the genetic association between immune responses and HLA.
2.We identified allergenic peptides that bind to HLA molecules and found that IgE production is inhibited by catepsin B.
3.We elucidated the differences in HLA A bound motifs between alleles that are or are not associated with high frequencies of autoimmune disease susceptibility.
4.We established monoclonal antibodies against a monocyte-specific antigen encoded by a gene that maps to the HLA region.
5.We cloned proteosome and associated genes which are involved in the production of antigenic peptides.
6.We found that Valpha14 TCR is necessary for NKT cell differentiation.
7.We found new aspects of the relationship between gammadeltaT cell proliferation and GvH reactions.
8.We found different transcription factors are used for Th1 and Th2 cytokine genes expression.
9.We found a new soluble factor involved in the suppression of antibody production.

Research Products

• [Publications] Nishimura H.: "IL-5 is a novel growth factor for murine T cells induced by Salmonella infection." J.Immunol.(in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Matsushita S.: "HLA-DQ-binding peptide motif.I.Comparative binding analysis of type II collagen-derived peptides to DR and DQ molecules of rheumatoid arthritis-susceptible and non-susceptible haplotypes." Int.Immunol.(in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] DeMartino G.M.: "Indentification,purification,and chracterization of a PA700-dependent actvator of the proteasome." J.Biol.Chem.(in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Mineta M.: "Contribution of HLA class I and class II alleles to the regulat of antibody production to hepatitis B surface antigen in humans." Int.Immunol.8. 525-531 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hori T.: "Japanese cedar pollinosis and HLA-DP5." Tissue Antigens. 47. 485-491 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Min W.: "Identification of an epitope for T cells correlated with antibo response to hepatitis B surface antigen in vaccinated humans." Human Immunol.46. 93-99 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Adachi Y.: "Positive selection of invariant V 14+ T cells by non-major histocompatibility complex-encoded class I-like molecules expressed on bone marrow derived cells." Proc.Natl.Acad.Sci.USA. 92. 1200-1204 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Masuda E.S.: "NFATx:a functional member of the NFAT family that is predominantly expressed in the thymus." Mol.Cell.Biol.15. 2697-2706 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Watanabe S.: "Granulocyte-macrophage colony stimulation factor dependent replication of polyoma virus replicon in hematopoietic cells:Analyses of receptor signals for reprication and transcription." J.Biol.Chem.270. 9615-9621 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sakai T.: "Host intestinal intraepithelial T lymphocytes present during acute graft-versus-host disease in mice may contribute to the development of enteropathy." Eur.J.Immunol.25. 87-91 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Noguchi M.: "The MHC class I-like Zn-2-glycoprotein gene maps to mouse chromosome 5." Immunogenetics. 42. 72-74 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Matsuoka S.: "A novel type of cell death of lymphocytes induced by a monoclonal antibody without participation of complement." J.Exp.Med.181. 2007-2015 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sudo T.: "Differences in MHC-class I self peptide repertoires among HLA-A2 subtypes." J.Immunol.155. 4749-4756 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Futaki G.: "Naturally processed HLA-DR9/DR53(DRB1*0901/DRB4*0101)-bound peptides." Immunogenetics. 42. 299-301 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fukagawa T.: "A boundary of long-range G+C% mosaic domains in the human MHC locus:pseudoautosomal boundary-like sequence exists near the boundary." Genomics. 25. 184-191 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Altmann D.M.: "The T cell respnse of HLA-DR transgenic mice to myelin basic protein and other antigens in the presence and absence of human CD4" J.Exp.Med.181. 867-875 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sumida T.: "Selective reduction of T cells bearing invariant V24JQ antigen receptor in patients with systemic sclerosis." J.Exp.Med.182. 1163-1168 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Suzuki G.: "Impaired CD28-mediated costimulation in anergic T cells." Int.Immunol.7. 37-43 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nishimura H., et al.: "IL-5 is a novel growth factor for nurine T cells induced by Salmonella infection." J.Immunol. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Matsushita S., et al.: "HLA-DQ-binding peptide motif.I.Comparative binding analysis of type II collagen-derived peptides to DR and DQ molecules of rheumatoid arthiritis-susceptible and non-susceptible haplotypes." Int.Immunol. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] DeMartino G.M., et al.: "Identification, purification, and characterization of a PA 700-dependent actvator of the proteasome." J.Boil.Chem.(in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Mineta M., et al.: "Contribution of HLA A class I and class II alleles to the regulation of antibody production to hepatitis B surface antigen in humans." Int.Immunol.8. 525-531 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hori T., et al.: "Japanese cedar pollinosis and HLA A-DP5." Tissue Antigens. 47. 485-491 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Min W., et al.: "Identification of an epitope for T cells correlated with antibody response to hepatitis B surface antigen in vaccinated humans." Human Immunol.46. 93-99 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Adachi Y., et al.: "Positive selection of invariant V 14+ T cells by non-major histocompatibility complex-encoded class I-like molecules expressed on bone marrow derived cells." Proc.Natl.Acad.Sci.USA. 92. 1200-1204 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] MaSuda E.S., et al.: "NFATx : a functional member of the NFAT family that is predominantly expressed in the thymus." Mol.Cell.Biol.15. 2697-2706 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Watanabe S., et al.: "Granulocyte-macrophage colony stimulation factor dependent replication of polyoma virus replicon in hematopoietic cells : analyzes of receptor signals for replication and transcription." J.Biol.Chem.270. 9615-9621 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sakai T., et al.: "Host intestinal intraepithelial T lymphocytes present during acute graft-versus-host desease in mice may contribute to the development of enteropathy." Eur.J.Immunol.25. 87-91 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Noguchi M., et al.: "The MHC class I-like Zn-2-glycoprotein gene maps to mouse chromosome 5." Immunogenetics. 42. 72-74 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Matsuoka S., et al.: "A novel type of cell death of lymphocytes induced by a nomoclonal antibody without participation of complement." J.Exp.Med.181. 2007-2015 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sudo T., et al.: "Differences in MHC-class I self peptide repertoires among HLA-A2 subtypes." J.Immunol.155. 4749-4756 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Futaki, G., et al.: "Naturally processed HIA-DR9/DR53 (DRB1^<**>0901/DRB4^<**>0101) -bound peptides." Immunogenetics. 42. 299-301 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fukugawa T., et al.: "A boundary of long-range G+C% mosaic domains in the human MHC locus : pseudoautosomal boundary-like sequence exists near the boundary." Genomics.25. 184-191 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Altmann D.M., et al.: "The T cell response of HLA-DR transgenic mice to myelin basic protein and other antigens in the presence and absence of human CD4." J.Exp.Med.181. 867-875 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sumida T., et al.: "Selective reduction of T cells bearing invariant C24JQ antigen receptor in patients with systemic sclerosis." J.Exp.Med.182. 1163-1168 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Suzuki G., et al.: "Impaired CD28-mediated costimulation in anergic T cells." Int.Immunol.7. 37-43 (1995)
  • Description: 「研究成果報告書概要(欧文)」より