Role of class II MHC bound antigenic peptide in the pathogenesis of inflammatory bowel disease.

• Project/Area Number: 15590676
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Osaka City University
• Principal Investigator: OSHITANI Nobuhide Osaka City University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (20231235)
• Co-Investigator(Kenkyū-buntansha): WATANABE Kenji Osaka City University, Graduate School of Medicine, Hospital Lecturer, 医学研究科, 病院講師 (70382041) ; 中村 志郎 大阪市立大学, 大学院・医学研究科, 講師 (50271185)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,100,000 (Direct Cost: ¥3,100,000); Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
• Keywords: Inflammatory bowel disease / Crohn's disease / ulcerative colitis / class II MHC / antigenic peptide / tandem mass analysis / amino acid sequence / 炎症性腸疾患 / HLA-DR / 抗ペプチド / HLA-DP / 免疫吸着カラム

Research Abstract

Isolation of antigenic peptides from the MHC-groove has contributed to the understanding of T cell immune responses. We already reported antigenic peptides isolated from human intestinal HLA-DR grove contained various enteral antigens.
However, naturally bound peptide ligands for HLA-DP have yet to be reported in clinical samples. We examined antigenic peptides bound to the HLA-DP as well as HLR-DR groove in human intestine by ion-trap tandem mass spectrometry equipped with online reverse-phase high performance liquid chromatography. We detected 7 HLA-DR associated peptides and 10 HLA-DP associated peptides from 4 controls, 4 patients with ulcerative colitis, and 9 patients with Crohn's disease. The calculated molecular masses (m/z) of these peptides reangesd from 1430.7 to 2987.3 and 1212.6 to 2105.0 representing 15 to 26 and 15 to 18 amino-acid residues from HLA-DR and HLA-DP associated peptides, respectively. Most of these parent proteins were exogenous proteins including Escherichia coli, and Carnorhabditis elegans. The present results suggest that in vivo antigen processing by antigen-presenting cells and T lymphocytes in human intestine are participated with exogenous antigen presentation.

Research Products

• [Journal Article] Dislocation of tight junction proteins without F-actin disruption in inactive Crohn's disease. (2005)
  • Author(s): Oshitani N, Watanabe K, Nakamura S, Fujiwara Y, Higuchi K, Arakawa T.
  • Journal Title: Int J Mol Med 15 Pages: 407-410
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Significance of increased proliferation of immature plasma cells in the appendix of patients with ulcerative colitlis. (2005)
  • Author(s): Kawachiya T, Oshitani N, Jinno Y, Watanabe K, Nakamura S, Fujiwara Y, Higuchi K, Maeda K, Nishiguchi Y, Hirakawa K, Matsumoto T, Arakawa T.
  • Journal Title: Int J Mol Med 15 Pages: 417-423
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mycobacterial trehalose 6, 6' -dimycolate preferentially induces type 1 helper T cell responses through signal transducer and activator of transcription 4 protein. (2005)
  • Author(s): Oiso R, Fujiwara N, Yamagami H, Maeda S, Matsumoto S, Nakamura S, Oshitani N, Matsumoto T, Arakawa T, Kobayashi K
  • Journal Title: MicrobPathogenesis 39 Pages: 35-43
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis. (2005)
  • Author(s): Nishikawa M, Oshitani N, Matsumoto T, Nishigami T, Arakawa T, Inoue M
  • Journal Title: Brit J Cancer 93 Pages: 331-337
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Augmented expression of secondary lymphoid tissue chemokine and EBII ligand chemokine in Crohn's disease. (2005)
  • Author(s): Kawashima D, Oshitani N, Jinno Y, Watanabe K, Nakamura S, Higuchi K, Arakawa T.
  • Journal Title: J Clin Pathol 58 Pages: 1057-1063
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Dislocation of tight junction proteins without F-actin disruption in inactive Crohn's disease. (2005)
  • Author(s): Oshitani N, Watanabe K, Nakamura S, Fujiwara Y, Higuchi K, Arakawa T
  • Journal Title: Int J Mol Med 15 Pages: 407-410
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Significance of increased proliferation of immature plasma cells in the appendix of patients with ulcerative colitis. (2005)
  • Author(s): Kawachiya T, Oshitani N, Jinno Y, Watanabe K, Nakamura S, Fujiwara Y, Higuchi K, Maeda K, Nishiguchi Y, Hirakawa K, Matsumoto T, Arakawa T
  • Journal Title: Int J Mol Med 15 Pages: 417-423
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mycobacterial trehalose 6,6'-dimycolate preferentially induces type 1 helper T cell responses through signal transducer and activator of transcription 4 protein. (2005)
  • Author(s): Oiso R, Fujiwara N, Yamagami H, Maeda S, Matsumoto S, Nakamura S, Oshitani N, Matsumoto T, Arakawa T, Kobayashi K
  • Journal Title: MicrobPathogenesis 39 Pages: 35-43
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis. (2005)
  • Author(s): Nisikawa M, Oshitani N, Matsumoto T, Nishigami T, Arakawa T, Inoue M
  • Journal Title: Brit J Cancer 93 Pages: 331-337
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn's disease. (2005)
  • Author(s): Kawashima D, Oshitani N, Jinno Y, Watanabe K, Nakamura S, Higuchi K, Arakawa T
  • Journal Title: J Clin Pathol 58 Pages: 1057-1063
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Dislocation of tight junction proteins without F-actin disruption in inactive Crohn's disease. (2005)
  • Author(s): Oshitani N, Watanabe K, Nakamura S, Fujiwara Y, Higuchi K, Arakawa T.
  • Journal Title: Int J Mol Med 1 Pages: 407-410
• [Journal Article] Mycobacterial trehalose 6,6'-dimycolate preferentially induces type 1 helper T cell responses through signal transducer and activator of transcription 4 protein. (2005)
  • Author(s): Oiso R, Rujiwara N, Yamagami H, Maeda S, Matsumoto S, Nakamura S, Oshitani N, Matsumoto T, Arakawa T, Kobayashi K
  • Journal Title: MicrobPathogenesis 39 Pages: 35-43
• [Journal Article] Augmented expression of secondary lymphoid of tissue chemokine and EBIl ligand chemokine in Crohn's disease. (2005)
  • Author(s): Kawashima D, Oshitani N, Jinno Y, Watanabe K, Nakamura S, Higuchi K, Arakawa T.
  • Journal Title: J Clin Pathol 58 Pages: 1057-1063
• [Journal Article] Significance of increased proliferation of immature plasma cells in the appendix of patients with ulcerative colitis. (2005)
  • Author(s): Tomohiro Kawachiya, Nobuhide Oshitani, et al.
  • Journal Title: International journal of molecular medicine 15 Pages: 417-423
• [Journal Article] Dislocation of tight junction proteins without F-actin disruption in inactive Crohn｀s disease. (2005)
  • Author(s): Nobuhide Oshitani, Kenji Watanabe, et al.
  • Journal Title: International journal of molecular medicine 15 Pages: 407-410
• [Publications] Oshitani N et al.: "Analysis of intestinal HLA-DR bound peptides and dysregulated immunre responses to enteric flora in the pathogenesis of inflammatory bowel disease"Int J Mol Med. 11. 99-104 (2003)
• [Publications] Sawa Y, Oshitani N et al.: "Comprehensive analysis of intestinal cytokine messenger RNA profile by real-time quantitative polymerase chain reaction in patients with inflammatory bowel disease"Int J Mol Med. 11. 175-179 (2003)