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

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)-gamma ELISpot assay in 31 patients with autoimmune 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-gamma 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.