title: Identification of T cell epitopes on soluble liver antigen in Chinese patients with auto-immune hepatitis.
abstract: OBJECTIVE
  To identify soluble liver antigen (SLA)-specific dominant epitopes and analyse the correlation between SLA-specific T cell response and the status of the disease.
  
  
  METHODS
  A cross-sectional analysis of SLA-specific T cell responses to 54 overlapping peptides covering the entire SLA sequence was performed using an interferon (IFN)-γ ELISpot assay in 31 patients with auto-immune hepatitis (AIH)-1, 15 patients with primary biliary cirrhosis, 16 hepatitis B virus, seven hepatitis C virus infection and 10 healthy subjects, in order to assess the correlation between SLA-specific T cell responses and the clinical outcome.
  
  
  RESULTS
  Soluble liver antigen-specific IFN-γ responses in AIH were significantly more frequent in AIH patients (58.1%) than those in controls (6.7% in PBC, P=0.001; 4.3% in hepatitis B/C, P<0.001 and 0% in healthy subjects, P=0.0015). Among 31 AIH patients, the frequency of recognition and the magnitude of response to SLA peptides in anti-SLA antibody-positive patients were higher and stronger than those negative for anti-SLA antibodies (P=0.02 and 0.037 respectively). We further analysed T-cell restriction and found that six individual SLA peptides (4, 9, 11, 12, 41 and 44) were recognized by CD4 T cells, and the most frequently recognized peptides were peptides 12 (61.1% of participants), followed by peptide 4 and peptide 44 (55.6 and 38.9% respectively). Moreover, a positive association was found between the breadth of recognition of SLA peptides and the indices of liver damage.
  
  
  CONCLUSIONS
  T cell response to SLA in Chinese patients with AIH is broad and associated with hepatocyte damage.
authors: Clinical Research Centre for Autoimmune Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors: Yan
authors: Y
authors: Zhao
authors: Yonghong
authors: Y
authors: Zhang
authors: Yan-min
authors: YM
authors: Liu
authors: Yan
authors: Y
authors: Liu
authors: Xia
authors: X
authors: Feng
authors: Hui-yu
authors: HY
authors: Liao
authors: Diego
authors: D
authors: Vergani
authors: Yun
authors: Y
authors: Ma
authors: Hui-ping
authors: HP
authors: Yan
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D001219:Aspartate Aminotransferases / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D002681:China; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D019693:Hepatitis, Autoimmune / Q000201:enzymology / Q000208:ethnology / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D016056:Immunodominant Epitopes; C046431:liver antigen LA-1; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases