Stress-induced cell surface expression and antigenic alteration of the Ro/SSA autoantigen.

Stress-induced cell surface expression and antigenic alteration of the Ro/SSA autoantigen.
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应激诱导的细胞表面表达和 Ro/SSA 自身抗原的抗原改变。

DOI:
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发表时间:
1995
期刊:
影响因子:
3.5
通讯作者:
M. Yamamoto
M. Yamamoto
中科院分区:
医学4区
文献类型:
--
作者:
T. Igarashi;Y. Itoh;Y. Fukunaga;M. Yamamoto

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最近的研究表明Ro/SSA自身抗原是异质性的。有两个亚型家族; 60 kD形式(Ro 60)和52 kD形式(Ro 52)。最近我们发现抗Ro/SSA蛋白的自身抗体具有构象依赖性。抗Ro 60抗体主要针对天然蛋白质,相反地,抗Ro 52抗体仅针对变性蛋白质。已知对培养的角质形成细胞的UV照射诱导Ro/SSA的细胞表面表达,并且该现象被认为与具有抗Ro/SSA抗体的患者的光敏性有关。我们研究了热休克和紫外线照射等应激诱导的Ro/SSA蛋白质的定量和定性变化,发现无论是热休克还是紫外线照射,都只能在人外周血淋巴细胞表面表达Ro 52。此外,流式细胞仪分析显示,HS处理和UV处理的淋巴细胞可以被患者血清染色,并且通过使用免疫沉淀和Western免疫印迹相结合的技术,证实细胞表面表达的Ro 52可以被天然形式的抗Ro/SSA抗体识别,而细胞质Ro 52无法被识别。这些数据表明,Ro 52可以在体内的细胞表面上表达时,抗原性,并可能解释直接组织损伤的抗Ro/SSA抗体的机制。
Recent studies have shown that Ro/SSA autoantigen is heterogeneous. There are two isoform families; the 60 kD forms (Ro60) and the 52 kD forms (Ro52). Recently we have found that autoantibodies to the Ro/SSA proteins are conformation dependent. Anti-Ro60 antibodies are mainly directed to the native protein and conversely anti-Ro52 antibodies are directed only to the denatured protein. It has been known that UV irradiation to cultured keratinocytes induces cell surface expression of Ro/SSA and this phenomenon has been thought to be related with photosensitivity in patients with anti-Ro/SSA antibodies. We studied the quantitative and qualitative changes of the Ro/SSA protein induced by stress, such as with heat shock and UV irradiation, and found that only Ro52 could be expressed on the cell surface of human peripheral lymphocytes by either heat shock or UV irradiation. Moreover, flow cytometric analysis revealed that HS-treated and UV-treated lymphocytes could be stained with patient sera, and by using a technique which combined immunoprecipitation and Western immunoblotting, it has been confirmed that Ro52 expressed on the cell surface can be recognized by anti-Ro/SSA antibodies in native form while cytoplasmic Ro52 cannot be recognized. These data suggest that Ro52 can be antigenic in vivo when expressed on the cell surface and may explain the mechanism of direct tissue damage by anti-Ro/SSA antibodies.
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