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白塞病中65 kDa热休克蛋白B细胞表位的识别

Recognition of B-cell epitopes of the 65 kDa HSP in Behçet's disease.

作者信息

Direskeneli H, Hasan A, Shinnick T, Mizushima R, van der Zee R, Fortune F, Stanford M R, Lehner T

机构信息

Department of Immunology, Guy's Hospital, London, UK.

出版信息

Scand J Immunol. 1996 Apr;43(4):464-71. doi: 10.1046/j.1365-3083.1996.d01-53.x.

DOI:10.1046/j.1365-3083.1996.d01-53.x
PMID:8668927
Abstract

B-cell epitopes of the mycobacterial 65 kDa heat shock protein (HSP) were mapped in sera from patients with Behçet's Disease (BD). A series of 47 overlapping synthetic peptides (15ers) derived from the sequence of the Mycobacterium tuberculosis 65 kDa HSP was used in ELISA. Significant increases in IgA and IgG antibody levels were observed with peptides 111-125, 154-172 and 311-326 in sera from BD, compared with those from controls. Homologous peptides derived from the sequence of the human mitochondrial 60 kDa HSP were then examined. Peptides 136-150 and 336-351 showed comparable results to the homologous mycobacterial peptides 111-125 and 311-326, respectively. The B-cell epitopes defined in this investigation overlap with the T-cell epitopes the authors have previously reported in BD. Inhibition studies are consistent with the view that antibodies to each of the three B-cell epitope peptides represent a small proportion of the total B-cell epitope repertoire elicited by the 65 or 60 kD HSP. Sequential antibody studies suggest that IgA and IgG antibody titres to one or all three peptides tested may increase during exacerbation of ocular disease. The functional role of these antibodies needs to be determined, but the peptides may be involved in the immunopathogenesis of BD as they can induce experimental uveitis in Lewis rats, which is a principal manifestation of BD.

摘要

对白塞病(BD)患者血清中的分枝杆菌65 kDa热休克蛋白(HSP)的B细胞表位进行了图谱分析。采用了一系列47个从结核分枝杆菌65 kDa HSP序列衍生而来的重叠合成肽(15肽)进行酶联免疫吸附测定(ELISA)。与对照组相比,BD患者血清中肽段111 - 125、154 - 172和311 - 326的IgA和IgG抗体水平显著升高。随后检测了从人线粒体60 kDa HSP序列衍生的同源肽。肽段136 - 150和336 - 351分别显示出与同源分枝杆菌肽段111 - 125和311 - 326相当的结果。本研究中确定的B细胞表位与作者之前在BD中报道的T细胞表位重叠。抑制研究结果支持以下观点:针对三种B细胞表位肽中每一种的抗体仅占由65或60 kD HSP引发的总B细胞表位库的一小部分。系列抗体研究表明,在眼部疾病加重期间,针对一种或所有三种测试肽的IgA和IgG抗体滴度可能会升高。这些抗体发挥的功能作用尚待确定,但这些肽可能参与了BD的免疫发病机制,因为它们能在Lewis大鼠中诱发实验性葡萄膜炎,而葡萄膜炎是BD的主要表现之一。

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