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

Characterization of novel antigens recognized by serum autoantibodies from anti-CD1 TCR-transgenic lupus mice.
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抗 CD1 TCR 转基因狼疮小鼠血清自身抗体识别的新抗原的表征。

DOI:
10.1002/eji.200324201
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发表时间:
2004
影响因子:
5.4
通讯作者:
Utz,PaulJ
Utz,PaulJ
中科院分区:
医学3区
文献类型:
--
作者:
Hueber,Wolfgang;Zeng,Defu;Sharpe,Orr;Robinson,WilliamH;Strober,Samuel;Utz,PaulJ

文献摘要

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在这项研究中,我们进一步描述了最近描述的抗CD 1自身反应性T细胞受体转基因小鼠狼疮模型(CD 1狼疮模型)中的体液自身免疫反应。 我们发现并表征了新的自身抗原,包括一种105 kDa的蛋白质(p105)和一种可能与p105相关的140个碱基对(bp)的新RNA分子,以及几种具有不同生化特性的其他因子。  在CD 1狼疮模型中,经致死剂量辐照的BALB/c/nu/nu小鼠静脉注射来自表达编码CD 1d自身反应性的TCRα和β转基因的供体BALB/c小鼠的分选骨髓细胞和分选脾T细胞。  注射单阳性(CD 4+和CD 8+)转基因细胞亚群的宿主产生了抗双链DNA抗体和狼疮样疾病。通过Western印迹和免疫沉淀分析血清。用生化和血清学方法鉴定抗原。来自12只CD 1狼疮小鼠中的5只(42%)的血清自身抗体免疫沉淀了一种105 kDa的蛋白质,称为p105。p105与约140 bp的小RNA相关。 抗p105自身抗体出现在病程早期。血清学和生物化学特征表明,p105是不同于已知的狼疮自身抗原相似的分子量,表明p105代表一种新的自身抗原在狼疮。
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.