High-affinity binding of remyelinating natural autoantibodies to myelin-mimicking lipid bilayers revealed by nanohole surface plasmon resonance.
High-affinity binding of remyelinating natural autoantibodies to myelin-mimicking lipid bilayers revealed by nanohole surface plasmon resonance.
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纳米霍尔表面等离子体共振揭示了透明体自身抗体与髓鞘仿真脂质双层的高亲和力结合。
DOI：
10.1021/ac300819a
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发表时间：
2012-07-17
影响因子：
7.4
通讯作者：
Oh, Sang-Hyun
中科院分区：
文献类型：
--
作者：
Wittenberg, Nathan J.;Im, Hyungsoon;Xu, Xiaohua;Wootla, Bharath;Watzlawik, Jens;Warrington, Arthur E.;Rodriguez, Moses;Oh, Sang-Hyun
多发性硬化症是一种进行性神经系统疾病，其导致在中枢神经系统中隔离轴突的髓鞘降解。因此，促进髓鞘修复是多发性硬化症治疗研究的主要目标。两种小鼠单克隆天然自身抗体O 1和O 4在几种多发性硬化小鼠模型中促进髓鞘修复。天然自身抗体通常是多反应性的，并且主要是IgM同种型。流行的范例是，因为它们是多反应性的，所以这些抗体以低亲和力结合抗原。尽管它们在神经科学和神经胶质细胞研究中的广泛应用，然而，O 1和O 4抗体的亲和力和动力学常数至今尚未测定。在这项工作中，我们开发了一种膜生物传感平台的基础上，表面等离子体共振在金纳米孔阵列与一系列的表面修饰技术，形成髓鞘模拟脂质双层膜，以测量的协会和解离速率常数O 1和O 4抗体结合到他们的髓鞘脂质抗原。速率常数的比率表明，O 1和O 4结合半乳糖苷和硫酸化半乳糖苷，分别与天然自身抗体的异常小的表观解离常数（KD ~0.9 nM）。这比通常观察到的最高亲和力天然自身抗体低大约一到两个数量级。我们认为O 1和O 4与髓鞘中靶点的异常高亲和力有助于它们向少突胶质细胞发出信号并诱导中枢神经系统修复的机制。
Multiple sclerosis is a progressive neurological disorder that results in the degradation of myelin sheaths that insulate axons in the central nervous system. Therefore promotion of myelin repair is a major thrust of multiple sclerosis treatment research. Two mouse monoclonal natural autoantibodies, O1 and O4, promote myelin repair in several mouse models of multiple sclerosis. Natural autoantibodies are generally polyreactive and predominantly of the IgM isotype. The prevailing paradigm is that because they are polyreactive, these antibodies bind antigens with low affinities. Despite their wide use in neuroscience and glial cell research, however, the affinities and kinetic constants of O1 and O4 antibodies have not been measured to date. In this work, we developed a membrane biosensing platform based on surface plasmon resonance in gold nanohole arrays with a series of surface modification techniques to form myelin-mimicking lipid bilayer membranes to measure both the association and dissociation rate constants for O1 and O4 antibodies binding to their myelin lipid antigens. The ratio of rate constants shows that O1 and O4 bind to galactocerebroside and sulfated galactocerebroside, respectively, with unusually small apparent dissociation constants (KD ~0.9 nM) for natural autoantibodies. This is approximately one to two orders of magnitude lower than typically observed for the highest affinity natural autoantibodies. We propose that the unusually high affinity of O1 and O4 to their targets in myelin contributes to the mechanism by which they signal oligodendrocytes and induce central nervous system repair.
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影响因子：
8.4
作者：
Im H;Wittenberg NJ;Lesuffleur A;Lindquist NC;Oh SH
通讯作者：
Oh SH
影响因子：
64.8
作者：
Ebbesen, TW;Lezec, HJ;Wolff, PA
通讯作者：
Wolff, PA
影响因子：
3.9
作者：
Brolo, AG;Gordon, R;Kavanagh, KL
通讯作者：
Kavanagh, KL
DOI：
10.1016/0169-328x(95)00190-4
发表时间：
1995-12-28
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Asakura, K;Miller, DJ;Rodriguez, M
通讯作者：
Rodriguez, M
影响因子：
15.3
作者：
BURASTERO, SE;CASALI, P;NOTKINS, AL
通讯作者：
NOTKINS, AL