Majarian W R, Daly T M, Burns J M, Long C A
Department of Microbiology and Immunology, Hahnemann University, Philadelphia, Pennsylvania 19102.
Exp Parasitol. 1988 Dec;67(2):227-37. doi: 10.1016/0014-4894(88)90070-7.
We have previously identified and characterized a monoclonal antibody (McAb 302) with potent passive protective activity in mice infected with Plasmodium yoelii, a murine malarial parasite which depends on antibodies for resolution. To further study the appearance and regulation of this antibody during infection, we prepared syngeneic monoclonal antibodies specific for idiotopes present on McAb 302. Three hybridomas were established which synthesized antibodies that bound only to the homologous idiotype but which did not recognize isotypic specificities. All three of these antibodies were found to recognize distinct 302 idiotopes and two of these were shown to be specific for determinants associated with the antibody combining site of McAb 302. One of these monoclonal anti-idiotypic antibodies was used to develop an enzyme-linked immunosorbent assay for the 302 idiotype. When serum samples taken at different times from mice undergoing a primary infection with P. yoelii were tested in this assay, the 302 idiotype could not be detected even though the host was mounting a significant humoral response to the 230-kDa antigen recognized by McAb 302. These studies suggest that the idiotype of the protective McAb 302 is not a predominant one involved in the resolution of a P. yoelii infection and that only some idiotypes of antibodies directed to relevant plasmodial antigens possess significant biological activity. Therefore, protective immunization with plasmodial antigens may require the elicitation of selected idiotypes. Attempts to alter the course of P. yoelii infection by preimmunization with monoclonal or polyclonal anti-idiotypic reagents were unsuccessful.
我们之前已鉴定并表征了一种单克隆抗体（McAb 302），它在感染约氏疟原虫（一种依赖抗体来清除的鼠疟原虫）的小鼠中具有强大的被动保护活性。为了进一步研究该抗体在感染过程中的出现及调控情况，我们制备了针对McAb 302上独特型的同基因单克隆抗体。建立了三个杂交瘤，它们合成的抗体仅与同源独特型结合，但不识别同种型特异性。发现所有这三种抗体都能识别不同的302独特型，其中两种被证明对与McAb 302抗体结合位点相关的决定簇具有特异性。其中一种单克隆抗独特型抗体被用于开发针对302独特型的酶联免疫吸附测定法。当用该测定法检测从初次感染约氏疟原虫的小鼠在不同时间采集的血清样本时，即使宿主对McAb 302识别的230-kDa抗原产生了显著的体液反应，也检测不到302独特型。这些研究表明，保护性McAb 302的独特型并非参与清除约氏疟原虫感染的主要独特型，且只有一些针对相关疟原虫抗原的抗体独特型具有显著的生物学活性。因此，用疟原虫抗原进行保护性免疫可能需要激发选定的独特型。用单克隆或多克隆抗独特型试剂进行预免疫以改变约氏疟原虫感染进程的尝试未成功。
