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一种源自易患狼疮小鼠的独特单克隆抗体,它与多种与风湿性疾病相关的自身抗原具有多重结合。

A unique monoclonal antibody derived from a lupus-prone mouse with multiple bindings to autoantigens associated with rheumatic disease.

作者信息

Kanai Y, Yaoita Y, Imaoka K, Honjo T

机构信息

Department of Molecular Oncology, University of Tokyo, Japan.

出版信息

Immunol Lett. 1988 Sep;19(1):15-20. doi: 10.1016/0165-2478(88)90113-7.

Abstract

Monoclonal anti-poly(ADP-ribose) (MRP-2) was primarily a product of a hybridoma selected by binding to poly(ADP-ribose) from an autoimmune MRL/Mp-lpr/lpr (MRL/1) mouse. Detailed examination revealed that anti-poly(ADP-ribose) monoclonal IgMK antibody bound not only to left-handed Z-DNA and single-stranded (ss) DNA but also to a conformational epitope formed by histone and double-stranded (ds) DNA. A reconstitution study revealed that association of dsDNA with histone H3 plus H4 was essential for their binding to MRP-2 monoclonal antibody. MRP-2 monoclonal antibody acted as a rheumatoid factor (RF). Since some monoclonal or polyclonal human serum antibodies of rheumatoid arthritis (RA) or mixed connective tissue disease (MCTD) have been reported to recognize shared epitopes of denatured IgG and DNA-histone (nucleosomes), this MRP-2 monoclonal antibody with the similar activity derived from a lupus-prone mouse will be useful for the studies on the etiology of autoantibodies associated with RA, MCTD and systemic lupus erythematosus (SLE).

摘要

单克隆抗聚(ADP - 核糖)(MRP - 2)最初是一种杂交瘤产物,该杂交瘤是通过与来自自身免疫性MRL/Mp - lpr/lpr(MRL/1)小鼠的聚(ADP - 核糖)结合而筛选出来的。详细检查发现,抗聚(ADP - 核糖)单克隆IgMK抗体不仅能与左手螺旋Z - DNA和单链(ss)DNA结合,还能与由组蛋白和双链(ds)DNA形成的构象表位结合。一项重组研究表明,双链DNA与组蛋白H3加H4的结合对于它们与MRP - 2单克隆抗体的结合至关重要。MRP - 2单克隆抗体具有类风湿因子(RF)的作用。由于据报道类风湿关节炎(RA)或混合性结缔组织病(MCTD)的一些单克隆或多克隆人血清抗体可识别变性IgG和DNA - 组蛋白(核小体)的共同表位,这种源自易患狼疮小鼠且具有类似活性的MRP - 2单克隆抗体将有助于研究与RA、MCTD和系统性红斑狼疮(SLE)相关的自身抗体的病因。

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