ANTIBODY RESPONSES AGAINST MYELIN OLIGODENDROCYTE GLYCOP

该提案的长期目标是开发一种针对非人灵长类动物脱髓鞘EAE的新免疫学方法。 为了实现这一长期目标，将追求以下具体目标：（1）在C.雅克斯 使用基于PCR的方法RACE和随后的DNA测序将允许鉴定C。Jacchus IgG1 H和L链亚家族。 (2)分析了C.雅克斯 通过构建C. jacchus IgG mRNA，将有可能选择MOG和MBP特异性克隆，并描述在对这些髓鞘蛋白的抗体应答中IgG1 VH和VL κ的多样性使用。 (3)在MOG免疫的C. jacchus以防止脱髓鞘。 从选择用于与MOG或MBP高亲和力结合的噬菌体克隆中去除gIII蛋白将允许可溶性F[ab]片段的表达。 将测试高亲和力MOG特异性F[ab]预防绒猴EAE脱髓鞘的能力。 MBP特异性F[ab]将用作对照。如果这种免疫疗法被证明是成功的，那么基于类似原理的治疗方法就可以开发用于人类MS。

The long-term objective of this proposal is to develop a new immunotherapeutic approach towards demyelinating EAE in a non- human primate. To achieve this long-term goal the following specific aims will be pursued: (1) Characterization the IgG1 VH and VL kappa repertoire in C. jacchus. Using the PCR based method RACE and subsequent DNA sequencing will permit the identification of C. jacchus IgG1 H and L chain subfamilies. (2) Analysis of the diversity of the antibody response against myelin proteins in C. jacchus. By constructing a combinatorial F(ab) library from C. jacchus IgG mRNA it will be possible to select MOG and MBP specific clones and to describe the diversity IgG1 VH and VL kappa usage in the antibody response to these myelin proteins. (3) Production of soluble MOG-and MBP-specific F(ab) fragments to be administered in MOG immunized C. jacchus to prevent demyelination. The removal of the gIII protein from the phage clones selected for high affinity binding to MOG or MBP, will permit the expression of soluble F[ab] fragments. High affinity MOG specific F[ab] will be tested in their ability to prevent demyelination in marmoset EAE. MBP specific F[ab] will be used as control. If this immunotherapeutic approach proves to be successful, therapies based on similar principles could be developed for human MS.