In the past we identified immunogenic amino acid sequences within the liver soluble liver antigen/liver-pancreas antigen (SLA/LP) in humanized mice that are transgenic for HLA-DRB1*0301 and negative for murine MHC class II and were immunized with human SLA/LP. We tested antibody and T cell responses of the immunized mice and established T cell hybridoma to identify the minimal optimal DRB1*0301-restricted peptides (epitopes) within SLA/LP. These epitopes were then used to generate fluorescently labeled tetrameric complexes of DRB1*0301 and epitope peptides for ex vivo detection of murine autoantigen-specific T cells by flow cytometry. We have continued to use the identified T cell epitopes and tetramers to analyze the immune response of patients with anti-SLA/LP+ AIH. As specificity controls, PBMC from an HLA-DRB1*0301- patient with anti-SLA/LP+ AIH and HLA-DRB1*0301+, anti-SLA/LP- patients with past history of hepatitis B were studied in parallel. The frequency of tetramer-positive antigen-specific, CD4+ T cells detectable by Elispot and tetramer analysis in peripheral blood mononuclear cells of patients with anti-SLA/LP+ AIH was in the same range as frequencies of antigen-specific CD4+ T cells reported for other autoimmune diseases such as type I diabetes (Oling et al., J Autoimmun 2005) and chronic infectious diseases such as mycobacterium tuberculosis (Hohn et al., Scand J Immunol 2007), borrelia burgdorferi (Meyer et al., Proc Natl Acad Sci U S A 2000) and HCV infection (Day et al., J Clin Invest 2003;Ulsenheimer et al., J Viral Hepat 2006). The identified SLA/LP-specific T cell epitopes and their corresponding tetramers should therefore be useful to monitor AIH-specific T cells during acute AIH and active disease progression and to study their role in the liver, the site of this disease. We have continued to collect, isolate and cryopreserve peripheral blood mononuclear cells from patients with AIH who are prospectively followed during disease exacerbations and treatment, and will study them once a suitable panel of samples is collected.
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