IDIOTYPES AND INFLAMMATORY DEMYELINATION

这个建议是基于一个前提，即独特型（LD）和抗LD 神经网络参与中枢神经系统的炎性脱髓鞘， 多发性硬化症和实验性过敏性神经系统 脑脊髓炎 据推测，有一个共享的lds 致脑炎T细胞上发现的T细胞受体与抗体之间 髓鞘碱性蛋白（MBP）肽。 通过免疫接种， 互补肽，即，一种由RNA编码的肽， 目的肽或表位的mRNA，具有选择性的抗Id， 可以产生特异性。 这些抗lds抗体能够调节 体外体液和细胞免疫活性。 进一步 这些抗-LD的体外作用的表征和分析 它们在体内对免疫病理过程的影响是 这个提议。 具体目标是：（1）确定机制 单克隆抗-LD通过其抑制小鼠的合成， 带有针对MBP肽的单克隆抗体的Id的杂交瘤。 (2)到 表征抗Id对表达a的T细胞系和克隆的作用， T细胞受体的克隆型识别相同的MBP肽， LD单克隆抗体。 (3)以确定抗LD的效果 与针对致脑炎MBP肽乙酰基1-9的Id反应， PL/J小鼠实验性变态反应性脑脊髓炎的发生 (4)为了确定用与下述互补的肽免疫的效果， MBP肽乙酰基1-9对实验性变态反应的诱导作用 PL/J小鼠脑脊髓炎。 (5)以确定外周血B 细胞、EB病毒转化的B细胞、血清或脑脊液 从正常人，多发性硬化症或其他神经系统疾病的人 分泌或含有与选择人MBP反应的携带LD的抗体 缩氨酸 这次调查的结果将提供信息 与全身性疾病的天然或治疗诱导的调节相关， 或在炎症脱髓鞘中的原位免疫反应， 多发性硬化 随着对致脑炎序列的了解， MBP或另一种分子，使用互补肽或抗Id可 允许发展非致脑炎性，临床上可行 治疗剂。

This proposal is based on the premise that idiotype (ld) and anti-ld networks are involved in the inflammatory demyelination of the central nervous system which occurs in multiple sclerosis and experimental allergic encephalomyelitis. It is hypothesized that there is a sharing of lds between the T cell receptor found on encephalitogenic T cells and antibody to the dame myelin basic protein (MBP) peptide. Through immunization with a complementary peptide, i.e., a peptide encoded by RNA complementary to the mRNA of the peptide or epitope of interest, an anti-ld with selective specificity can be produced. These anti-lds are capable of modulating humoral and cellular immune activities in vitro. The further characterization of the in vitro effects of these anti-lds and the analysis of their in vivo impact on immunopathological processes are the goals of this proposal. The specific aims will be: (1) to define the mechanism through which monoclonal anti-ld inhibits the synthesis by murine hybridomas of ld-bearing monoclonal antibodies to MBP peptides. (2) to characterize the effect of anti-ld on T cell lines and clones expressing a T cell receptor whose clonotype recognizes the same MBP peptide as does the ld-bearing monoclonal antibody. (3) to determine the effect of anti-ld reacting with the ld against the encephalitogenic MBP peptide acetyl 1-9 on the development of experimental allergic encephalomyelitis in PL/J mice. (4) to determine the effect of immunization with a peptide complementary to MBP peptide acetyl 1-9 on the induction of experimental allergic encephalomyelitis in PL/J mice. (5) to determine if peripheral blood B cells, Epstein-Barr virus transformed B cells, serum or cerebrospinal fluid from normals, persons with multiple sclerosis or other neurological disease secrete or contain ld-bearing antibody reactive with selected human MBP peptides. The results of this investigation will furnish information relevant to the natural or therapeutically induced modulation of a systemic or in situ immune response in inflammatory demyelination as occurs in multiple sclerosis. With the knowledge of an encephalitogenic sequence of MBP or another molecule, the use of complementary peptides or anti-lds may permit the development of non-encephalitogenic, clinically feasible therapeutic agents.