Two monoclonal antibodies generated against human hsp60 show reactivity with synovial membranes of patients with juvenile chronic arthritis
Two monoclonal antibodies generated against human hsp60 show reactivity with synovial membranes of patients with juvenile chronic arthritis
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针对人 hsp60 产生的两种单克隆抗体显示出与幼年慢性关节炎患者滑膜的反应性
DOI：
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发表时间：
1992
影响因子：
15.3
通讯作者：
W. Eden
中科院分区：
文献类型：
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作者：
Claire J. P. Boog;Elisabeth K. de Graeff;M. Lucassen;R. Zee;Marleen M. Voorhorst;P. Kooten;H. Geuze;W. Eden
热休克蛋白已被证明是许多自身免疫性疾病的关键抗原。在人类关节炎和实验诱导的动物关节炎中，疾病的发展被认为与针对细菌Hsp60以及针对其哺乳动物同系物的免疫反应的发展是一致的。我们用重组人热休克蛋白60免疫小鼠，制备了鼠源性单抗。选择对哺乳动物HSP60具有独特特异性的抗体，与细菌对应物(LK1)不发生交叉反应，以及识别人和细菌HSP60(LK2)的抗体。这两种抗体都识别位于人类Hsp60的383和447位氨基酸之间的表位。免疫金电镜示Hsp60在HepG2细胞中的线粒体定位。此外，LK1和LK2在幼年慢性关节炎患者滑膜的光镜免疫组织化学中均显示出较高的染色水平。LK1对哺乳动物Hsp60具有独特的特异性，因此LK1的染色增加明确地表明，这是由于内源性产生的宿主Hsp60表达水平的提高，而不是细菌抗原的沉积。
Heat-shock proteins have been shown to be critical antigens in a number of autoimmune diseases. In human arthritis and in experimentally induced arthritis in animals, disease development was seen to coincide with development of immune reactivity directed against not only bacterial hsp60, but also against its mammalian homologue. We have developed murine monoclonal antibodies after immunization with recombinant human hsp60. Antibodies with unique specificity for mammalian hsp60, not crossreactive with the bacterial counterpart (LK1), and antibodies recognizing both human and bacterial hsp60 (LK2) were selected. Both antibodies recognize epitopes located between amino acid positions 383 and 447 of human hsp60. In immunogold electron microscopy, the mitochondrial localization of hsp60 in HepG2 cells was shown. Furthermore, both LK1 and LK2 showed a raised level of staining in light microscopy immunohistochemistry of synovial membranes in patients with juvenile chronic arthritis. The increased staining for LK1, with a unique specificity for mammalian hsp60, thus unequivocally demonstrates that this is due to a raised level of expression of endogenously produced host hsp60 and not to deposition of bacterial antigens.