Melino M R, Epstein S L, Sachs D H, Hansen T H
J Immunol. 1983 Jul;131(1):359-64.
The serologic lesion of the I-A mutant mouse strain, bm12, was investigated with the use of monoclonal anti-Iab antibodies and anti-idiotypic (Id) reagents produced against these antibodies. In a fluorometric analysis, three different monoclonal anti-Iab antibodies (25-9-17, 34-5-3, 28-16-8) failed to bind bm12 cells, whereas two anti-Iab antibodies (25-5-16 and 17/227), which bound bm12 cells, showed about one-half the fluorescence intensity that they showed in binding to Iab antigens. Of the three monoclonal antibodies that failed to react with bm12 cells, two antibodies (25-9-17 and 34-5-3) were found to bind the same steric site on Iab molecules (cluster I). In contrast, the antibodies (25-5-16 and 17/227) that reacted with both Iab and Iabm12 antigens were found to bind a second distinct site (cluster II). The binding of antibody 28-16-8 to Iab antigens inhibited reciprocally the binding of cluster I and II anti-Iab antibodies, suggesting a possible third site, sterically located intermediate between the other two sites. To assess the relatedness of the antibodies defining the serologic lesion of bm12 mice, xenogeneic and syngeneic anti-Id reagents were produced against antibodies 25-9-17 and 28-16-8. By using these anti-Ids in a binding site-related inhibition assay, a cross-reactive idiotype was detected that is shared by 25-9-17 and 34-5-3 antibodies; thus these two monoclonal antibodies share several features, including 1) idiotypic determinants, 2) failure to bind bm12 cells, 3) binding the same spatial Iab site, and 4) having indistinguishable serologic fine specificity that corresponds with a previously defined predominant alloantigenic determinant recognized in the bm12 anti-Iab humoral response. Therefore, several parameters of antibody recognition of Ia can now be correlated with structural changes in Ia molecules. These findings will potentiate future studies of the T cell recognition of these same Ia epitopes.
利用单克隆抗Iab抗体和针对这些抗体产生的抗独特型（Id）试剂，对I-A突变小鼠品系bm12的血清学损伤进行了研究。在荧光分析中，三种不同的单克隆抗Iab抗体（25-9-17、34-5-3、28-16-8）未能与bm12细胞结合，而两种与bm12细胞结合的抗Iab抗体（25-5-16和17/227），在与Iab抗原结合时显示出的荧光强度约为其一半。在三种未与bm12细胞反应的单克隆抗体中，发现两种抗体（25-9-17和34-5-3）结合Iab分子上的同一空间位点（簇I）。相反，与Iab和Iabm12抗原均反应的抗体（25-5-16和17/227）被发现结合第二个不同的位点（簇II）。抗体28-16-8与Iab抗原的结合相互抑制簇I和II抗Iab抗体的结合，提示可能存在第三个位点，在空间上位于其他两个位点之间。为了评估定义bm12小鼠血清学损伤的抗体之间的相关性，针对抗体25-9-17和28-16-8产生了异种和同基因抗Id试剂。通过在结合位点相关抑制试验中使用这些抗Id试剂，检测到一种交叉反应独特型，其为25-9-17和34-5-3抗体所共有；因此，这两种单克隆抗体具有几个共同特征，包括1）独特型决定簇，2）未能与bm12细胞结合，3）结合相同的Iab空间位点，4）具有难以区分的血清学精细特异性，这与先前在bm12抗Iab体液反应中识别的主要同种异型抗原决定簇相对应。因此，现在可以将Ia抗体识别的几个参数与Ia分子的结构变化相关联。这些发现将促进未来对这些相同Ia表位的T细胞识别研究。
