HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Identification of CD4 T-cell epitopes in soluble liver antigen/liver pancreas autoantigen in autoimmune hepatitis.

AbstractBACKGROUND & AIMS:
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with autoantibodies and liver-infiltrating lymphocytes. Although autoantibodies are tested routinely to diagnose and classify AIH, liver-infiltrating lymphocytes are regarded as the primary factor for disease pathogenesis. The purpose of this study was to identify and characterize autoantigenic peptides within human AIH-specific soluble liver antigen/liver pancreas antigen (SLA/LP) that are targeted by CD4(+) T cells and restricted by the disease susceptibility gene HLA-DRB1*0301.
METHODS:
HLA-DRB1*0301 transgenic mice were immunized with SLA/LP. Antibody and T-cell responses were analyzed with SLA/LP-overlapping peptides in enzyme immunoassay, proliferation, and enzyme-linked immunospot (ELISpot) assays. Minimal optimal T-cell epitopes were identified, characterized with cloned T-cell hybridomas, and confirmed in tetramer and ELISpot assays with AIH patients' peripheral blood mononuclear cells.
RESULTS:
All mice developed SLA/LP-specific IgG1/IgG2a antibodies against the same SLA/LP peptides as human beings. T cells targeted several peptides within SLA/LP, 2 of which were DR3-restricted and one overlapped the sequence recognized by human autoantibodies. Minimal optimal epitopes were mapped, DRB1*0301/epitope-tetramers were generated, and the frequency and function of HLA-DRB1*0301-restricted autoantigen-specific T cells in AIH patients were analyzed with tetramer and interferon-gamma ELISpot assays.
CONCLUSIONS:
This study identified T-cell epitopes within SLA/LP, restricted by the disease susceptibility gene DRB1*0301 and in close proximity to the human autoantibody epitope. These results and the generated reagents now provide the opportunity to directly monitor autoreactive T cells in AIH patients in clinical studies.
AuthorsHeiko Mix, Christina Weiler-Normann, Robert Thimme, Golo Ahlenstiel, Eui-Cheol Shin, Johannes Herkel, Chella S David, Ansgar W Lohse, Barbara Rehermann
JournalGastroenterology (Gastroenterology) Vol. 135 Issue 6 Pg. 2107-18 (Dec 2008) ISSN: 1528-0012 [Electronic] United States
PMID18773898 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Autoantibodies
  • Autoantigens
  • Epitopes, T-Lymphocyte
  • liver antigen LA-1
Topics
  • Adult
  • Aged
  • Animals
  • Autoantibodies (immunology, metabolism)
  • Autoantigens (immunology, metabolism)
  • CD4-Positive T-Lymphocytes (immunology)
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte (immunology, metabolism)
  • Female
  • Hepatitis, Autoimmune (immunology, pathology)
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Middle Aged
  • Young Adult

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: