al-Balaghi S, Abedi-Valugerdi M, Möller E
Department of Immunology, Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Scand J Immunol. 1996 Nov;44(5):470-7. doi: 10.1046/j.1365-3083.1996.d01-338.x.
The immunological specificites of two human rheumatoid factor-reactive IgG monoclonal antibodies derived from unstimulated rheumatoid synovial lymphocytes have been analysed. A malaria antigen-reactive IgG monoclonal antibody from an immune donor served as a control. Purified IgG monoclonal antibody from one IgG-RF hybridoma (L1), but not from the other IgG-RF hybridoma (D1) or the anti-malaria monoclonal antibody, exhibited dose-dependent binding to multiple self and non-self antigens such as ds-DNA, cytochrome-c, bovine thyroglobulin, transferrin, cellulose and lipopolysaccharide and therefore was considered polyreactive. The immunological specificity was confirmed by inhibition experiments using the same soluble antigens as inhibitors. The polyreactivity of the IgG-RF MoAb was markedly inhibited by absorption with glycoproteins such as thyroglobulin, a commonly used target for xenoreactive natural antibodies, and cytochrome-c, indicating that the monoclonal antibody is reactive with epitopes expressed on these ligands. Since some naturally occurring antibodies are carbohydrate specific, the authors tested the IgG-RF MoAb for possible carbohydrate specificity. Absorption with certain polysaccharides containing only one or two different sugar moieties did not inhibit the binding reactivities to any of the tested antigens. Polyreactivity of the monoclonal antibody, unlike most xenoreactive natural antibodies, was not caused by reactivity with (gal alpha 1-3gal) as indicated by the remaining binding reactivity after alpha-galactosidase treatment of the antigen. Removal of the N-linked glycosylation sites within the Fc portion of target IgG markedly reduced the antibody binding. The findings suggest that the carbohydrate content of the antigen is necessary for binding of the polyreactive IgG-RF MoAb. Reactivity to carbohydrate antigens may readily explain the so-called multispecificity of certain antibodies.
对源自未经刺激的类风湿性滑膜淋巴细胞的两种人类风湿因子反应性IgG单克隆抗体的免疫特异性进行了分析。来自免疫供体的一种疟疾抗原反应性IgG单克隆抗体用作对照。来自一个IgG-RF杂交瘤（L1）的纯化IgG单克隆抗体，而非另一个IgG-RF杂交瘤（D1）或抗疟疾单克隆抗体，表现出与多种自身和非自身抗原（如双链DNA、细胞色素c、牛甲状腺球蛋白、转铁蛋白、纤维素和脂多糖）的剂量依赖性结合，因此被认为具有多反应性。使用相同的可溶性抗原作为抑制剂的抑制实验证实了其免疫特异性。IgG-RF单克隆抗体的多反应性被甲状腺球蛋白等糖蛋白和细胞色素c吸收后显著抑制，甲状腺球蛋白是异种反应性天然抗体常用的靶点，这表明该单克隆抗体与这些配体上表达的表位具有反应性。由于一些天然存在的抗体具有碳水化合物特异性，作者测试了IgG-RF单克隆抗体是否具有可能的碳水化合物特异性。用仅含有一两种不同糖部分的某些多糖吸收并不抑制对任何测试抗原的结合反应性。与大多数异种反应性天然抗体不同，单克隆抗体的多反应性不是由与（半乳糖α1-3半乳糖）的反应性引起的，这一点通过对抗原进行α-半乳糖苷酶处理后仍保留的结合反应性得以表明。去除目标IgG的Fc部分内的N-连接糖基化位点显著降低了抗体结合。这些发现表明，抗原的碳水化合物含量对于多反应性IgG-RF单克隆抗体的结合是必要的。对碳水化合物抗原的反应性可能很容易解释某些抗体的所谓多特异性。
