Establishment of a polyreactive T cell clone from Asian type multiple sclerosis patients and identification of the responsible antigens

亚洲型多发性硬化症患者多反应性 T 细胞克隆的建立及相关抗原的鉴定

基本信息

批准号：
10470154
负责人：
KIRA Jun-ichi
金额：
$ 6.08万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

In Japanese, we previously reported the existence of two subtypes of multiple sclerosis (MS), namely, Asian type MS, in which the clinically estimated lesions are confined to the optic nerves and spinal cord, and Western type MS showing disseminated lesions in the CNS including the cerebrum, cerebellum and brainstem. In the present study, sixty-four myelin overlapping peptides consisting of 16-21 residues which correspond to the human MBP, PLP and MOG sequences were synthesized and myelin peptide specific autoreactive CD4+T cell lines were established by stimulating PBMC with these peptides from MS patients and healthy controls. MS patients tended to show epitope spreading in autoreactive CD4+T cell lines as compared with healthy controls. Reactivity against the mixture of overlapping peptides derived from each myelin proteins was then determined. The results indicated that reactivity to MOG was predominant as Asian type MS. On the other hand, Western type MS showed response to all mye … More lin proteins examined. It has been previously reported that the lesions were confined to the optic nerves and spinal cord in BN rats sensitized with MOG. These findings may indicate that predominant reactivity to MOG in Asian type MS may contribute to the development of opticospinal from MS. Furthermore, DP5(DPA1ィイD1*ィエD102022/DPBAィイD1*ィエD10501) restricted autoreactive CD4+T cell clone (SS1. 2) was established in Asian type MS. SS1.2 recognized 196MBP peptide p74-93 and 170MPB peptide p47-67 and responded to the recombinant 170MBP protein. We investigated responses of SS1.2 to analog peptides with single amino acid substitution. It was found that residues 84 (position 1(p1)), 86(p3), 87(p4), 89(p6) and 90(p7) of the peptide were critical for its binding to DP5 molecule and recognition by TCR. On the basis of these observations, we are going to establish an expression library system for searching peptides recognized by the autoreactive CD4+T cells from DP5 positive Asian type MS patients, we expect that specific antigens in Asian type MS could be explored by such a system in future, Less

在日语中，我们的存在是两个扇形病（MS）的亚型，限于视神经和脊髓，西方类型的MS在CNS中显示了包括大脑，小脑和脑干在内的中枢神经系统中的传播病变。，合成了由16-21个残留物D的16-21个残留物D组成的髓磷脂重叠的肽，合成了与人MBP，PLP和MOG序列合成，并通过使用这些肽的PBMC刺激PBMC来确定MS患者和健康对照组的PBMC，从而确定髓磷脂特异性自身反应性CD4+T细胞系。与健康对照相比，MS患者在自动反应性CD4+T细胞系中的表现散布与从每个髓磷脂蛋白中得出的重叠肽的反应性相比手，西部类型MS对所有MYE的反应，以前是在BN大鼠中使用MOG敏感的绳索。 *Yi D102022/DPBA II D1*Yi D10501）在亚洲类型的SS1.2女士中建立了限制的自动反应性CD4+T细胞克隆（SS1。2）蛋白质。我们研究了SS1.2的反应，发现居民84（位置1（p1），86（P3），89（p6）通常对其与DP5分子结合和TCR识别至关重要在DP5阳性亚洲型MS患者的自动反应性CD4+T细胞所认识的观察结果中，我们希望将来可以通过这种系统来探索亚洲类型MS中的特定抗原，较少