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

在日本，我们先前曾报道过多型多发性硬化症（MS）的两个亚型的存在，命名为亚洲型多发性硬化症，在临床上估计的问题被确认为光学神经和脊柱神经，以及西方型多发性硬化症显示在中枢神经系统中的分离问题，包括Cerebellum和Brainstem。在目前的研究中，16-21个驻地的64个骨髓蛋白重叠肽对人类MBP、PLP和MOG序列是合成的和特定于骨髓蛋白的自动活性CD 4 +T细胞线通过刺激性PBMC和这些肽和健康控制。MS患者倾向于显示epitope在自动CD 4 +T细胞线上传播，与健康控制相比较。对重叠肽的混合反应是从每个骨髓蛋白质中提取出来的，然后就被确定了。根据研究结果，MOG对MOG的反应被认为是亚洲型MS，在另一边，西方型MS显示了对所有我的反应 ... More 林蛋白质被测试了。它曾被报道过，该系列被认为是BN老鼠对MOG敏感的光学神经和脊柱神经。These findings may indicate that predominant reactivity to MOG in Asian type MS may contributes to the Oracle of opticospinal from MS。Furthermore， DP5（DPA 1イD1* イD102022/DPBAイD1 * イD10501） restricted autoreactive CD4+T cell clone （SS1。2）已在亚洲型MS.SS1.2中确定了196 MBP肽p74-93和170 MPB肽p47-67，并响应于重组170 MBP蛋白。我们对SS1.2的模拟肽的反应进行了研究，以单个氨基酸替代。在TCR下发现了84 （第1页）、86（第3页）、87（第4页）、89（第6页）和90（第7页）的肽对DP 5分子和识别的结合至关重要。关于这些观察的基础，我们将建立一个表达式库系统，用于搜索由DP 5阳性亚洲型MS患者识别的肽的自动CD 4 +T细胞，我们预计亚洲型MS中的特定抗原可以通过未来的系统来解释，少

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