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模型单克隆免疫复合物与人类红细胞CR1受体相互作用中的同型和克隆变异。

Isotypic and clonal variations in the interactions between model monoclonal immune complexes and the human erythrocyte CR1 receptor.

作者信息

Yokoyama I, Waxman F

机构信息

Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.

出版信息

Mol Immunol. 1992 Jul-Aug;29(7-8):935-47. doi: 10.1016/0161-5890(92)90132-h.

DOI:10.1016/0161-5890(92)90132-h
PMID:1386141
Abstract

Erythrocytes (E) play a central role in handling circulating immune complexes (IC) in primates. E capture IC via complement receptors, type 1 (CR1) which can bind to C3b and C4b ligand sites generated on IC during activation of the complement cascade. The present study was designed to explore how the immunochemical properties of IC affected their interactions with human E. Model IC were constructed by combining murine monoclonal anti-dinitrophenyl (DNP) antibodies with DNP-bovine serum albumin. A panel of 10 independently-derived monoclonal IgG1, IgG2a, IgG2b, IgG3, IgM and IgA antibodies were used to construct IC and their interactions with human E were examined in vitro. The data reveal that IC constructed with the different monoclonal antibodies differed with respect to their rate of binding to E, the peak magnitude of IC binding to E, and the rate and extent of IC release from E. IC containing IgG1 antibodies (IgG1 IC), IgG2a IC, IgG2b IC, and IgA IC all bound rapidly to E, whereas IgG3 IC and IgM IC were bound relatively slowly to E. The peak magnitude of IC binding to E correlated directly with their binding rate. There was an inverse correlation between the antigen/antibody ratio of the IC and the magnitude of IC binding to E. The rate of release of the various types of IC from E also differed. IgG2a IC and IgG2b IC displayed the most rapid maximum release rates while IgG3 IC had the slowest peak release rate. IgM IC and IgA IC were also released relatively slowly from E. IgG1 IC had an intermediate release rate. There was no direct correlation between the maximum release rate and either the maximum binding rate or the peak magnitude of IC binding to E. While there were some clonotypic differences in binding and release rates between IC made with different IgG2a, IgG3 and IgM antibodies, antibody isotype appears to be of fundamental importance with respect to both the binding of IC to E and the release of IC from E. These data indicate that the immunochemical properties of IC can profoundly affect their interactions with human E and that the panel of IC constructed with monoclonal antibodies can serve as a useful model to explore these interactions.

摘要

红细胞(E)在灵长类动物处理循环免疫复合物(IC)的过程中发挥着核心作用。红细胞通过补体受体1(CR1)捕获IC,CR1能够与补体级联激活过程中在IC上产生的C3b和C4b配体位点结合。本研究旨在探讨IC的免疫化学特性如何影响其与人类红细胞的相互作用。通过将鼠单克隆抗二硝基苯基(DNP)抗体与DNP - 牛血清白蛋白结合构建模型IC。使用一组10种独立衍生的单克隆IgG1、IgG2a、IgG2b、IgG3、IgM和IgA抗体构建IC,并在体外检测它们与人类红细胞的相互作用。数据显示,用不同单克隆抗体制备的IC在与红细胞的结合速率、IC与红细胞结合的峰值大小以及IC从红细胞上释放的速率和程度方面存在差异。含有IgG1抗体的IC(IgG1 IC)、IgG2a IC、IgG2b IC和IgA IC都能迅速与红细胞结合,而IgG3 IC和IgM IC与红细胞的结合相对较慢。IC与红细胞结合的峰值大小与其结合速率直接相关。IC的抗原/抗体比值与IC与红细胞结合的大小呈负相关关系。各种类型的IC从红细胞上释放的速率也有所不同。IgG2a IC和IgG2b IC表现出最快的最大释放速率,而IgG3 IC的峰值释放速率最慢。IgM IC和IgA IC从红细胞上的释放也相对较慢。IgG1 IC的释放速率处于中等水平。最大释放速率与最大结合速率或IC与红细胞结合的峰值大小之间没有直接相关性。虽然用不同的IgG2a、IgG3和IgM抗体制备的IC在结合和释放速率上存在一些克隆型差异,但抗体亚型对于IC与红细胞的结合以及IC从红细胞上的释放似乎至关重要。这些数据表明,IC的免疫化学特性可深刻影响其与人类红细胞的相互作用,并且用单克隆抗体制备的IC组可作为探索这些相互作用的有用模型。

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引用本文的文献

1
Clonal variations in complement activation and deposition of C3b and C4b on model immune complexes.补体激活的克隆变异以及C3b和C4b在模型免疫复合物上的沉积
Immunology. 1993 Oct;80(2):168-76.