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

In Japanese, we previously reported the existence of two subtypes of multiple sclerosis （MS）namely, Asian type MS，in clinically estimated lesions are confined to the optic nerves and spinal cord，Western类型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 humanmbp,PLP and MOG sequences were synthesized and myelin peptide specific autoreactive CD4+T cell lineswere established by stimulating PBMC with这些peptides from MS patients and healthy controls. MSpatients tended to show epitope spreading in autoreactive CD4+T cell lines as compared with healthycontrols. Reactivity against the mixture of overlapping peptides derived from each myelin proteins这是确定的。The results indicated that activity to MOG was predominant as Asian type MS.On the other hand, Western type MS showed response to all myeMore lin proteins examined.它已经预先报告了该课程的配置optic nerves and spinal cord in BN rats sensitized with MOG. These findings may indicate thatpredominant reactivity to MOG in Asian type MS may contribute to the development of opticospinalfrom MS. Furthermore，DP5(DPA1 - D1* D102022/DPBA - D1 - D10501) restricted autoreactive CD4+T cell clone (SS1. 2) wasestablished in Asian type MS. SS1.2 recognized 196mbp peptide p74-93 and 170mpb peptide p47-67 andresponded to the combinant 170mbp protein.我们投资的反应SS1.2 to analog peptideswith single amino acid substitution. It found that residues 84 (position 1(p1)), 86(p3)，87 (p4),89（p6）和90(p7) of the peptide were critical for its binding to DP5 molecule and recognition byTCR. On the basis of these observations我们要去建立一个表示法图书馆系统，用于搜索peptides recognized by theautoreactive CD4+T cells from DP5 positive Asian type MS patients，我们expect that specific antigens in Asian type MS could be explored by such a system in future， Less

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