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Identification of T cell epitopes on soluble liver antigen in Chinese patients with auto‐immune hepatitis
Author(s) -
Zhao Yan,
Zhang Yonghong,
Liu Yanmin,
Liu Yan,
Feng Xia,
Liao Huiyu,
Vergani Diego,
Ma Yun,
Yan Huiping
Publication year - 2011
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02487.x
Subject(s) - elispot , epitope , antigen , immunology , medicine , immune system , antibody , hepatitis , autoimmune hepatitis , cirrhosis , t cell , liver disease
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.