Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
J Immunol. 2011 Apr 1;186(7):4263-8. doi: 10.4049/jimmunol.1003934. Epub 2011 Feb 25.
For 15 y, α B-crystallin (heat shock protein [Hsp] B5) has been labeled an autoantigen in multiple sclerosis (MS) based on humoral and cellular responses found in humans and animal models. However, there have been several scientific inconsistencies with this assignment, ranging from studies demonstrating small differences in anticrystallin responses between patients and healthy individuals to the inability of crystallin-specific T cells to induce symptoms of experimental allergic encephalomyelitis in animal models. Experiments in this article demonstrate that the putative anti-HspB5 Abs from 23 MS patients cross-react with 7 other members of the human small Hsp family and were equally present in normal plasma. Biolayer interferometry demonstrates that the binding was temperature dependent, and that the calculated K(a) increased as the concentration of the sHsp decreased. These two patterns are characteristic of multiple binding sites with varying affinities, the composition of which changes with temperature, supporting the hypothesis that HspB5 bound the Ab and not the reverse. HspB5 also precipitated Ig heavy and L chains from sera from patients with MS. These results establish that small Hsps bind Igs with high affinity and refute much of the serological data used to assign α B-crystallin as an autoantigen.
15 年来，α B-晶状体蛋白（热休克蛋白 [Hsp] B5）一直被标记为多发性硬化症（MS）中的自身抗原，这基于在人类和动物模型中发现的体液和细胞反应。然而，这种分配存在一些科学上的不一致，从研究表明患者和健康个体之间的抗晶状体蛋白反应存在微小差异，到晶状体蛋白特异性 T 细胞无法在动物模型中诱导实验性过敏脑脊髓炎的症状，不一而足。本文中的实验表明，来自 23 名 MS 患者的假定抗-HspB5 Abs 与人类小 Hsp 家族的其他 7 个成员发生交叉反应，并且在正常血浆中同样存在。生物层干涉测量法表明，结合是温度依赖性的，并且随着 sHsp 浓度的降低，计算出的 K(a) 增加。这两种模式是具有不同亲和力的多个结合位点的特征，其组成随温度而变化，支持 HspB5 结合 Ab 而不是相反的假设。HspB5 还从 MS 患者的血清中沉淀 Ig 重链和轻链。这些结果证实小 Hsps 与 Ig 具有高亲和力结合，并反驳了用于将α B-晶状体蛋白鉴定为自身抗原的许多血清学数据。
