Artandi S E, Calame K L, Morrison S L, Bonagura V R
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):94-8. doi: 10.1073/pnas.89.1.94.
A combination of site-directed mutagenesis and exon exchange has been used to further define the structure on IgG recognized by monoclonal IgM rheumatoid factors (RFs) from patients with Waldenstrom macroglobulinemia. Most of these RFs bound IgG1, -2, and -4 but not IgG3. For these RFs, His-435 is a critical residue for binding and replacing it with arginine, the residue present in IgG3, destroys or reduces RF binding. However, additional polymorphic sequences in both the heavy-chain constant-region domains (CH) 2 and 3 are important for RF binding. Among the important residues in CH2 are amino acids 252-254 and 309-311, which are conserved among IgG isotypes and comprise two loops of amino acids on the surface of the domain. Therefore, at least three regions, two from CH2 and one from CH3, contribute significantly to the epitope recognized by the RFs. Although this epitope contains many of the same residues as the staphylococcal protein A binding site on IgG, the binding specificities of staphylococcal protein A and monoclonal RFs are not identical. Sera from patients with rheumatoid arthritis contain antibodies directed not only at this epitope but also at other sites on IgG.
定点诱变和外显子交换相结合的方法已被用于进一步确定由华氏巨球蛋白血症患者的单克隆 IgM 类风湿因子（RFs）识别的 IgG 上的结构。这些 RFs 大多与 IgG1、-2 和 -4 结合，但不与 IgG3 结合。对于这些 RFs，His-435 是结合的关键残基，用 IgG3 中存在的精氨酸取代它会破坏或降低 RF 结合。然而，重链恒定区结构域（CH）2 和 3 中的其他多态性序列对 RF 结合也很重要。CH2 中的重要残基包括氨基酸 252 - 254 和 309 - 311，它们在 IgG 同种型中保守，并且在该结构域表面构成两个氨基酸环。因此，至少三个区域，两个来自 CH2，一个来自 CH3，对 RFs 识别的表位有显著贡献。尽管该表位包含许多与 IgG 上葡萄球菌蛋白 A 结合位点相同的残基，但葡萄球菌蛋白 A 和单克隆 RFs 的结合特异性并不相同。类风湿性关节炎患者的血清中不仅含有针对该表位的抗体，还含有针对 IgG 上其他位点的抗体。
