Hillson J L, Karr N S, Oppliger I R, Mannik M, Sasso E H
Division of Rheumatology, University of Washington, Seattle 98195.
J Exp Med. 1993 Jul 1;178(1):331-6. doi: 10.1084/jem.178.1.331.
The ability of human VH3 immunoglobulins (Ig) to bind to staphylococcal protein A (SPA) via their Fab region is analogous to the binding of bacterial superantigens to T cell receptors. The present report establishes the structural basis for the interaction of SPA and VH3 Ig. We have studied a panel of 27 human monoclonal IgM that were derived from fetal B lymphocytes. As such, these IgM were expected to be encoded by unmutated germline genes. Binding to SPA in ELISA occurred with 15 of 15 VH3 IgM, but none of 12 IgM from the VH1, VH4, VH5, or VH6 families. The VH sequences of the 27 IgM were derived from 20 distinct VH elements, including 11 from the VH3 family. Use of D, JH, and CL genes was similar among VH3 and non-VH3 IgM. A comparison of the corresponding VH protein sequences, and those of previously studied IgM, identified a probable site for SPA binding that includes VH3 residues in framework region 3 (FR3), and perhaps FR1 and 3' complementary determining region 2. The results thus demonstrate that among human IgM, specificity for SPA is encoded by at least 11 different VH3 germline genes. Furthermore, like the T cell superantigens, SPA likely binds to residues in the VH framework region, outside the classical antigen-binding site of the hypervariable loops.
人类VH3免疫球蛋白（Ig）通过其Fab区域与葡萄球菌蛋白A（SPA）结合的能力类似于细菌超抗原与T细胞受体的结合。本报告确立了SPA与VH3 Ig相互作用的结构基础。我们研究了一组源自胎儿B淋巴细胞的27种人单克隆IgM。因此，预计这些IgM由未突变的种系基因编码。在ELISA中，15种VH3 IgM中有15种与SPA结合，但VH1、VH4、VH5或VH6家族的12种IgM均未与SPA结合。这27种IgM的VH序列源自20个不同的VH元件，其中11个来自VH3家族。VH3和非VH3 IgM之间D、JH和CL基因的使用情况相似。对相应的VH蛋白序列以及先前研究的IgM的序列进行比较，确定了一个可能的SPA结合位点，该位点包括框架区3（FR3）中的VH3残基，可能还有FR1和3'互补决定区2。因此，结果表明在人类IgM中，对SPA的特异性由至少11种不同的VH3种系基因编码。此外，与T细胞超抗原一样，SPA可能与VH框架区中高变环经典抗原结合位点之外的残基结合。
