IDIOTYPES AND INFLAMMATORY DEMYELINATION

独特型和炎症性脱髓鞘

• 批准号: 6302803
• 负责人: JOHN N WHITAKER
• 金额: $ 22.61万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6302803
• 关键词: B lymphocyte; CD4 molecule; T cell receptor; T lymphocyte; anergy; antiidiotype antibody; cerebrospinal fluid; clinical research; epitope mapping; experimental allergic encephalomyelitis; helper T lymphocyte; human subject; immunocytochemistry; immunoglobulin genes; immunoglobulin idiotypes; in situ hybridization; laboratory mouse; mass spectrometry; monoclonal antibody; multiple sclerosis; myelin basic proteins; myelinopathy; neuroimmunomodulation

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.

该提议基于偶像型（LD）和反世纪的前提 网络参与了中央的炎症性脱髓鞘 神经系统发生在多发性硬化症和实验过敏性中 脑脊髓炎。 假设有LDS共享 在脑源性T细胞和抗体上发现的T细胞受体之间 到髓磷脂基本蛋白（MBP）肽。 通过免疫 互补肽，即由RNA编码的肽 感兴趣的肽或表位的mRNA，一种具有选择性的抗LD 可以产生特异性。 这些抗LDS能够调节 体外的体液和细胞免疫活性。 进一步 表征这些抗LDS的体外效应和分析 他们的体内对免疫病理学过程的影响是 这个建议。 具体目的是：（1）定义机制 单克隆抗LLD抑制鼠的合成 含LD的单克隆抗体与MBP肽的杂交瘤。 （2）至 表征抗LD对表达T细胞系和克隆的影响 T细胞受体的克隆型与 含有LD的单克隆抗体。 （3）确定抗LD的影响 与LD反应与脑源性MBP肽乙酰基1-9在 PL/J小鼠中实验过敏性脑脊髓炎的发展。 （4）确定用肽互补的肽免疫的影响 MBP肽乙酰基1-9在诱导实验过敏 PL/J小鼠中的脑脊髓炎。 （5）确定外周血B 细胞，爱泼斯坦 - 巴尔病毒转化了B细胞，血清或脑脊液 来自正常的人，有多发性硬化症或其他神经系统疾病 用选定的人MBP分泌或包含含LD的抗体反应性 肽。 这项调查的结果将提供信息 与全身性的自然或治疗诱导的调节有关 或炎症性脱髓鞘中的原位免疫反应 多发性硬化症。 了解脑源序列 MBP或其他分子，使用互补肽或抗LDS可能 允许开发非脑化的，临床上可行的 治疗剂。