Identification of T cell epitopes on soluble liver antigen in Chinese patients with auto-immune hepatitis

• Published in: Liver international Vol. 31; no. 5; pp. 721 - 729
• Main Authors: Zhao, Yan, Zhang, Yonghong, Liu, Yan-min, Liu, Yan, Feng, Xia, Liao, Hui-yu, Vergani, Diego, Ma, Yun, Yan, Hui-ping
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2011
• Subjects: Adult; Aged; Asian Continental Ancestry Group; Aspartate Aminotransferases - blood; auto-immunity; Autoantibodies - blood; autoantibody; Autoantigens - immunology; Biomarkers - blood; Case-Control Studies; CD4-Positive T-Lymphocytes - immunology; Cells, Cultured; Chi-Square Distribution; China; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; epitopes; Epitopes, T-Lymphocyte; Female; hepatitis; Hepatitis, Autoimmune - enzymology; Hepatitis, Autoimmune - ethnology; Hepatitis, Autoimmune - immunology; HLA-DR Antigens - immunology; HLA-DRB1 Chains; Humans; Immunodominant Epitopes; Interferon-gamma - metabolism; Male; Middle Aged; Severity of Illness Index; T cells; China
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/j.1478-3231.2011.02487.x

Aim: 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. Conclusion: T cell response to SLA in Chinese patients with AIH is broad and associated with hepatocyte damage.