• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Identification and characterization of T cell epitope in primary biliary cirrhosis

Research Project

Project/Area Number 11694287
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

NAKAMURA Minoru (2001)  Medical Department, Kyushu University, Assistant, 医学部・附属病院, 助手 (40217906)

石橋 大海 (1999-2000)  九州大学, 医学研究院, 助教授 (80127969)

Co-Investigator(Kenkyū-buntansha) NISHIMURA Yasuharu  Kumamoto University, Graduate School of Medical Sciences, Professor, 大学院・医学系研究科, 教授 (10156119)
FUKUI Yoshinori  Kyushu University, Graduate School of Medical Sciences, Associate Professor, 医学研究院, 助教授 (60243961)
SASAZAKI Takehiko  Kyushu University, Graduate School of Medical Sciences, Professor, 医学研究院, 教授 (50014121)
MATSUSHITA Sho  Kumamoto University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学系研究科, 助教授 (50167649)
中村 稔  九州大学, 医学部・附属病院, 助手 (40217906)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordsprimary biliary cirrhosis / autoimmune disease / immune-regulation / antigen-specific immunotherapy / PDC-E2 / molecular mimicry / analogue peptide / mitochondrial antigen / 原発性胆汁性肝研変 / 抗ミトコンドリア抗体 / MHC / ペプチド複合体 / 分子相同性 / 自己免疫疾患
Research Abstract

In patients with primary biliary cirrhosis (PBC), the anti-mitochondrial antibody response is primarily directed against E2 components of the pyruvate dehydrogenase complex (PDC-E2), 2-oxoglutarate dehydrogenase complex (OGDC-E2), the branched chain 2 oxo-acid dehydrogenase complex (BCOADC-E2), and the E3 binding protein (E3BP) of PDC. We have previously demonstrated that the PDC-E2 163-176 peptide (GDLLAEIETDKATI) is the immunodominant autoreactive T cell epitope which is restricted by HLA DR53 (DRA1^*0101/DRB4^*0101). To address the issue of molecular mimicry and cross-recognition among mitochondrial antigens, we analyzed the reactivity to a series of single amino acid substituted peptides of ten cloned T cell lines derived from both healthy subjects and patients with PBC which recognize a single T cell receptor (TCR) ligand, PDC-E2 163-176 peptide/HLA DR53. In addition, we performed antagonism and agonism assays using analogue peptides to determine the most critical TCR contact resi … More due(s). Our data demonstrate that the overall fine specificities are unique for every single T cell clone but that these T cell clones are roughly categorized into two distinct groups based on their recognition motifs of TCR ligand ; the ^<170>ExDK^<173> (group A) and the ^<168>EIExD^<172> (group B). ^<170>E is the most critical TCR contact residue for both groups of cloned T cell lines whereas ^<173>K and ^<168>E are critical TCR contact residues for group A and group B cloned T cell lines, respectively. Importantly, both group A and group B T cell clones were established from the peripheral blood of both patients with PBC and healthy subjects. Most importantly, some of the group A cloned T cell lines cross-react to human E3BP 34-47, human OGDC-E2 100-113, and several peptides derived from various microbial proteins carrying an ExDK motif, while group B cloned T cell lines react only to E3BP 34-47 carrying an EIExD motif. Furthermore, an RGxG motif was exclusively found in the complementarity determining region (CDR3) of the TCR Vβ in the group B cloned T cell lines, while G, S, and/or R were frequently found in the CDR3 of the TCR Vβ in the group A cloned T cell lines. These data may provide a molecular basis for understanding molecular mimicry and cross-recognition among mitochondrial antigens in PBC. Less

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Fukushima, N., Ikematsu, H..Nakamura, M., et al.: "Nucleotide variations amongst V, genes of AMA-producing B cell clones in primary biliary cirrhosis"Journal of Autoimmunity. 14・3. 247-257 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimoda, S., Nakamura, M., Shigematsu H., et al.: "Mimicry peptides of human PDC-E2 163-176 peptide, the immunodominant T-cell epitope of primary biliary cirrhosis"Hepatology. 31・6. 1212-1216 (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., et al.: "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・5. 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] Nishio, A., Keeffe, E.B., Ishibashi, H., et al.: "Diagnosis and treatment of primary biliary cirrhosis"Medical Sci ence Monitoring. 6・1. 181-193 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 中村稔, 下田慎治, 石橋大海: "原発性胆汁性肝硬変(PBC)におけるT細胞認識抗原の多様性と交差認識"日本臨床免疫学会会誌. 23・6. 221-226 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishibashi, H.: "Are PBC and AIC reflective of the pendulum of a clock and therefore represent a "phase" of the same disease?"Journal of Gastroenterolory Hepatology. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishibashi, H., et al.: "Autoimmune Liver Disease -Its Recent Advances"Elsevier Science B.V.. 264 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishibashi, H., Shigematsu, H., Shimoda, S., Nakamura, M.: "Antigen peptide analog - Induction of T cell anergy in primary biliary cirrhosis"Internal Medicine. 38(2). 173-175 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Quaranta, S., Van de Water, J., Ishibashi, H., Rosina, F., Coppel, R., Gershwin, M.E.: "The immunopathogenesis of primary biliary cirrhosis"Hepato-Gastroenterol. 46. 3041-3047 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishio, A., Keeffe, E.B., Ishibashi, H., Gershwin, M.E.: "Diagnosis and treatment of primary biliary cirrhosis"Med Sci Monit. 6(1). 181-193 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukushima, N., Ikematsu, H., Nakamura, M., Matsui, M., Shimoda, S., Hayashida, K., Niho, Y., Koike, K., Gershwin, M.E., Ishibashi, H.: "Nucleotide variations amongst VH genes of AMA-producing B cell clones in primary biliary cirrhosis"J Autoimmunity. 14(3). 247-257 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishio, A., Coppel, R., Ishibashi, H., Gershwin, M.E.: "The pyruvate dehydrogenase complex as a target autoantigen in primary biliary cirrhosis. in Diagnosis and treatment of primary biliary cirrhosis. Bailliere's Best Practice & Research"Clinical Gastroenterology. 14(4). 535-547 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimoda, S., Nakamura, M., Shigematsu, H., Tanimoto, H., Gushima, T., Gershwin, M.E., Ishibashi, H.: "Mimicry peptides of human PDC-E2 163-176 peptide, the immunodominant T-cell epitope of primary biliary cirrhosis"Hepatology. 31(6). 1212-1216 (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, M.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(5). 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] Tanaka A, Borchers AT, Ishibashi H, Ansarif AA, Gershwin ME: "Genetic and familial considerations of primary biliary cirrhosis"Am J Gastroenterol. 96(1). 8-15 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishibashi H: "Are primary biliary cirrhosis and autoimmune cholangitis reflective of the pendulum of a clock and therefore represent a 'phase' of the same disease?"J Gastroenterol Hepatol. 16(2). 121-123 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishibashi H, Kamihira T, Shimoda S.: "Bile duct cell apoptosis : a rare event in primary biliary cirrhosis?"Digest Liver Dis. 33(2). 122-124 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Van de Water J, Ishibashi H, Coppel RL, Gershwin ME: "Molecular mimicry and primary biliary cirrhosis : Premises not promises"Hepatology. 33(4). 771-775 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukushima, N., Ikematsu H., Nakamura, M.et al.: "Nucleotide varisticms amongst Vhgenes of AHA-producing Bcell clones in primary biliary cirrhosis"Journal of Autoimmunity. 14・3. 247-257 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimoda, S., Nakamura, M.et al.: "Mimicry peptide of human PDC-E2 163-176 peptide, the immunodominant T-cell epitope of primary biliany cirrhosis"Hepatology. 31・6. 1212-1216 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shigematsu, H., Shimoda, S., Nakamura, M.et al.: "Fine specificity of Tcells reactive to human PDC-E2 163-176 peptide, the immunodominant autoantigen in primary biliary cirrhosis"Hepatology. 32・5. 901-909 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 中村稔, 下田慎治, 石橋大海: "原発性胆汁性肝硬変におけるT細胞認識抗原の多様性と交差反応"日本臨床免疫学会会誌. 23・6. 221-226 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukushima,N.,Ikematsu,H.,Nakamura,M., et al.: "Nucleotide variations amongst V_H genes of AMA-producing B cell clones in primary biliary cirrhosis."Journal of Autoimmunity. 14・3. 247-257 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shimoda,S.,Nakamura,M.,Shigematsu,H., et al.: "Mimicry peptides of human PDC-E2 163-176 peptide, the immunodominant T-cell epitope of primary biliary cirrhosis."Hepatology. 31・6. 1212-1216 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigematsu,H.,Shimoda,S.,Nakamura,M., et al.: "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・5. 901-909 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishio,A.,Keeffe,E.B.,Ishibashi,H., et al.: "Diagnosis and treatment of primary biliary cirrhosis."Medical Sci ence Monitoring. 6・1. 181-193 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 中村稔,下田慎治,石橋大海: "原発性胆汁性肝硬変(PBC)におけるT細胞認識抗原の多様性と交差認識"日本臨床免疫学会会誌. 23・6. 221-226 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishibashi,H.: "Are PBC and AIC reflective of the pendulum of a clock and therefore represent a "phase" of the same disease?"Journal of Gastroenterolory Hepatology. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishibashi,H., et al.: "Autoimmune Liver Disease-Its Recent Advances"Elsevier Science B.V.. 264 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishio,A.,Coppel,R.,Ishibashi,H., et al.: "Best Practice & Research, Clinical Gastroenterology 14(4): 2000 "primary biliary cirrhosis""Bailliere Tindall. 687 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishibashi,H.,et al: "Antigen peptide analog: Induction of T cell anergy in primary biliary cirrhosis"Internal Medicine. 38・2. 173-175 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Quaranta,S.,et al: "The immunopathogenesis of primary biliary cirrhosis"Hepato-Gastroenterology. 46・1. 1-7 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kinoshita,H.,et al: "Autoimmune cholangitis and primary biliary cirrhosis.-An autoimmune enigma"Liver. 19・1. 122-128 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takasaki,S.,et al: "Elevated serum soluble CD8 level in autoimmune hepatitis and the effect of corticosteroid therapy"Hepatology Research. 15・1. 52-63 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishibashi,H.,et al: "Progress in Hepatology,Vol.5 Liver and Immunology"Yamanaka,M.,Toda,G.,Tanaka,T.. 150 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishibashi,H.,et al: "自己抗体と自己免疫Autoantibodies and Autoimmunity'99"山本一彦,高崎芳成,三森経世,Jack D Keene. 55 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Dubel,L.,et al: "Disease of the Liver and the Bile Ducts-New Aspects and Clinical Implications"Paumgarter,P.. 250 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 重松宏尚,他: "消化器と免疫 No.35"日比紀文,名倉 宏,淀井淳司,茂呂 周,西岡幹夫,島村和男. 230 (1999)

    • Related Report
      1999 Annual Research Report

URL: 

Published: 1999-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi