Salvetti M, Ristori G, Buttinelli C, Fiori P, Falcone M, Britton W, Adams E, Paone G, Grasso M G, Pozzilli C
Department of Neurological Sciences, Università La Sapienza, v. le dell'Università, Rome, Italy.
J Neuroimmunol. 1996 Apr;65(2):143-53. doi: 10.1016/0165-5728(96)00013-6.
Heat shock proteins (HSP) are the most conserved molecules known to date that may also function as immune targets during infection. Hence, theoretically there is a high chance of cross-reactive responses to epitopes shared by host and microbe HSP. If not properly regulated, these responses may contribute to the pathogenesis of autoimmune disease. To determine if immune responses to HSP could contribute to the pathogenesis of multiple sclerosis, we raised T lymphocyte lines specific for the purified protein derivative of Mycobacterium tuberculosis (PPD) from patients with multiple sclerosis, patients with tuberculosis and from healthy individuals. These lines were then screened for their proliferative response to a M. tuberculosis 70-kDa heat shock protein (M.tb.HSP70). The relative frequency of the recognition of highly conserved sequences of M.tb.HSP70 compared to variable ones was also assessed by mapping experiments on those PPD specific T lymphocyte lines which also recognized the mycobacterial 70-kDa heat shock protein. In patients with multiple sclerosis, we observed a significantly higher estimated frequency of PPD-specific T lines responding to M.tb.HSP70 compared to healthy individuals and patients with tuberculosis. Furthermore, mapping experiments using recombinant proteins representing mycobacterial and human HSP70 sequences and a panel of synthetic peptides encompassing the whole sequence of Mycobacterium leprae HSP70, showed that the response to conserved epitopes of HSP70 is a frequent event in each of the three conditions studied, often leading to the cross-recognition of microbial and human sequences. These findings implicate the 70-kDa heat shock proteins as potential autoantigens in multiple sclerosis.
热休克蛋白（HSP）是迄今为止已知的最保守的分子，在感染过程中也可能作为免疫靶点发挥作用。因此，从理论上讲，对宿主和微生物HSP共有的表位产生交叉反应的可能性很大。如果这些反应没有得到适当调节，可能会导致自身免疫性疾病的发病机制。为了确定对HSP的免疫反应是否会导致多发性硬化症的发病机制，我们从多发性硬化症患者、结核病患者和健康个体中培养了针对结核分枝杆菌纯化蛋白衍生物（PPD）的T淋巴细胞系。然后筛选这些细胞系对结核分枝杆菌70 kDa热休克蛋白（M.tb.HSP70）的增殖反应。通过对那些也识别分枝杆菌70 kDa热休克蛋白的PPD特异性T淋巴细胞系进行定位实验，还评估了与可变序列相比，M.tb.HSP70高度保守序列的识别相对频率。在多发性硬化症患者中，我们观察到与健康个体和结核病患者相比，对M.tb.HSP70有反应的PPD特异性T系估计频率显著更高。此外，使用代表分枝杆菌和人类HSP70序列的重组蛋白以及一组涵盖麻风分枝杆菌HSP70全序列的合成肽进行的定位实验表明，在研究的三种情况中的每一种情况下，对HSP70保守表位的反应都是常见事件，常常导致对微生物和人类序列的交叉识别。这些发现表明70 kDa热休克蛋白是多发性硬化症中潜在的自身抗原。
