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针对小鼠抗CD4单克隆抗体的抗独特型抗体的免疫化学和功能特性分析

Immunochemical and functional characterization of anti-idiotypic antibodies to a mouse anti-CD4 monoclonal antibody.

作者信息

Perosa F, Dannecker G, Ferrone S, Dammacco F

机构信息

Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Italy.

出版信息

Int J Clin Lab Res. 1991;21(2):179-85. doi: 10.1007/BF02591640.

Abstract

Immunization of BALB/c mice with the mouse anti-CD4 monoclonal antibody (mAb) HP2/6 resulted in the production of anti-idiotypic antibodies. Analysis of the kinetics of the development of anti-idiotypic antibodies showed a homogeneous response among the immunized animals. Cross-blocking assays performed with anti-CD4 mAbs OKT4, OKT4c and OKT4d showed that syngeneic anti-idiotypic antiserum elicited with mAb HP2/6 recognizes idiotope(s) expressed only on the immunizing mAb. The idiotope(s) is (are) located within or closely related to the antigen-combining site of mAb HP2/6. Hybridization with the myeloma cell line NSO of splenocytes from a BALB/c mouse hyperimmunized with mAb HP2/6 generated the anti-idiotypic mAbs F11-2113, F11-2302 and F11-2444 which recognize idiotope(s) outside the antigen-combining site of mAb HP2/6. Although the anti-idiotypic mAbs cross-inhibit each other in their binding to mAb HP2/6, they differ in the ability to elicit anti-anti-idiotypic antisera. Furthermore, mAb F11-2113 enhances CD4 down-regulation in the presence of mAb HP2/6 to a larger extent than mAbs F11-2302 and F11-2444. The latter results suggest an additional mechanism by which anti-idiotypic antibodies may induce functional abnormalities of CD4+ T cells in human immunodeficiency virus-infected T cells.

摘要

用小鼠抗CD4单克隆抗体(mAb)HP2/6对BALB/c小鼠进行免疫可产生抗独特型抗体。对抗独特型抗体产生动力学的分析表明,免疫动物之间的反应具有同质性。用抗CD4单克隆抗体OKT4、OKT4c和OKT4d进行的交叉阻断试验表明,由mAb HP2/6诱导产生的同基因抗独特型抗血清识别仅在免疫单克隆抗体上表达的独特型表位。该独特型表位位于mAb HP2/6的抗原结合位点内或与之密切相关。用mAb HP2/6高度免疫的BALB/c小鼠的脾细胞与骨髓瘤细胞系NSO杂交,产生了抗独特型单克隆抗体F11-2113、F11-2302和F11-2444,它们识别mAb HP2/6抗原结合位点以外的独特型表位。尽管抗独特型单克隆抗体在与mAb HP2/6结合时相互交叉抑制,但它们在诱导抗抗独特型抗血清的能力上有所不同。此外,在存在mAb HP2/6的情况下,mAb F11-2113比mAb F11-2302和F11-2444更能增强CD4的下调。后一结果提示了一种额外的机制,通过该机制抗独特型抗体可能在人类免疫缺陷病毒感染的T细胞中诱导CD4+T细胞的功能异常。

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