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一种模拟脂多糖(LPS)内核决定簇结构的抗独特型单克隆抗体的研制。

Development of an anti-idiotype monoclonal antibody mimicking the structure of lipopolysaccharide (LPS) inner-core determinants.

作者信息

Field S, Pollack M, Morrison D C

机构信息

Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City 66160.

出版信息

Microb Pathog. 1993 Aug;15(2):103-20. doi: 10.1006/mpat.1993.1061.

Abstract

An anti-idiotype antibody has been developed which is specific for idiotypic determinants of a BALB/c mouse IgG3 monoclonal antibody (MAbY1-4A6) directed against the inner-core Kdo region of lipopolysaccharide (LPS). Armenian hamsters were immunized with MAbY1-4A6 and splenocytes from immunized animals fused with Sp2/0 myeloma cells. Eight clones secreting antibodies that bound to MAbY1-4A6, but not control IgG3, were identified and subcloned. Culture supernatants from one hybridoma, termed MAb4G2, contain monoclonal antibody that binds to the variable region of MAbY1-4A6 and dose-dependently inhibits binding of MAbY1-4A6 to Re chemotype rough mutant LPS (Re-LPS). This antibody also inhibits binding of three additional mouse monoclonal antibodies specific for the inner-core of Re-LPS. MAb4G2 also recognizes a significant proportion of antibodies present in polyclonal R-chemotype antisera generated in mice (Re-LPS) and rabbits (J5 Rc-LPS). Mice and hamsters immunized with MAb4G2 or Re-LPS generate antibodies which cross-react with both immunogens. Cumulatively, these data suggest that MAb4G2 can function as an internal image of the Kdo-specific monoclonal antibody, MAbY1-4A6, mimicking the antigenic structure and immunogenicity of a portion of the LPS inner-core Kdo region.

摘要

已开发出一种抗独特型抗体,它对针对脂多糖(LPS)内核Kdo区域的BALB/c小鼠IgG3单克隆抗体(MAbY1-4A6)的独特型决定簇具有特异性。用MAbY1-4A6免疫亚美尼亚仓鼠,并将免疫动物的脾细胞与Sp2/0骨髓瘤细胞融合。鉴定并亚克隆了八个分泌与MAbY1-4A6结合但不与对照IgG3结合的抗体的克隆。来自一个称为MAb4G2的杂交瘤的培养上清液含有与MAbY1-4A6可变区结合的单克隆抗体,并能剂量依赖性地抑制MAbY1-4A6与Re化学型粗糙突变体LPS(Re-LPS)的结合。该抗体还能抑制另外三种对Re-LPS内核具有特异性的小鼠单克隆抗体的结合。MAb4G2还能识别在小鼠(Re-LPS)和兔子(J5 Rc-LPS)中产生的多克隆R化学型抗血清中存在的相当一部分抗体。用MAb4G2或Re-LPS免疫的小鼠和仓鼠产生的抗体与两种免疫原都发生交叉反应。总体而言,这些数据表明MAb4G2可以作为Kdo特异性单克隆抗体MAbY1-4A6的内影像,模拟LPS内核Kdo区域一部分的抗原结构和免疫原性。

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