Characterization of novel antigens recognized by serum autoantibodies from anti-CD1 TCR-transgenic lupus mice

Authors

  • Wolfgang Hueber,

    1. Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, USA
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  • Defu Zeng,

    1. Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, USA
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  • Orr Sharpe,

    1. Veterans Affairs Palo Alto Health Care System, Palo Alto, USA
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  • William H. Robinson,

    1. Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, USA
    2. Veterans Affairs Palo Alto Health Care System, Palo Alto, USA
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  • Samuel Strober,

    1. Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, USA
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  • Paul J. Utz

    Corresponding author
    1. Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, USA
    • Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, CCSR Room 2215A, Stanford, CA 94305, USA Fax: +1-650-723-7509
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Abstract

In this study, we further characterize the humoral autoimmune response in the recently described anti-CD1 autoreactive T cell receptor-transgenic mouse lupus model (CD1 lupus model). We discovered and characterized novel autoantigens, comprising a protein of 105 kDa (p105) and a novel RNA molecule of 140 base pairs (bp) that is likely associated with p105, and several additional factors with distinct biochemical properties. In the CD1 lupus model, lethally irradiated BALB/c/nu/nu mice were injected intravenously with sorted bone marrow cells and sorted splenic T cells from donor BALB/c mice expressing TCR α and β transgenes that encode autoreactivity for CD1d. Adoptive hosts injected with the single-positive (CD4+ and CD8+) subset of transgenic cellsdeveloped anti-double-stranded DNA antibodies and a lupus-like illness. Sera were analyzed by Western blotting and immunoprecipitation. Antigens were characterized by biochemical and serological methods. Serum autoantibodies from 5 of 12 (42%) CD1 lupus mice immunoprecipitated a 105-kDa protein, termed p105. p105 was associated with a small RNA of ∼140 bp. Anti-p105 autoantibodies appeared early in the course of disease. Serological and biochemical characterization suggested that p105 was distinct from known lupus autoantigens of similar molecular masses, indicating that p105 represents anovel autoantigen in lupus.

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