Study of antigen receptors and peptide recognition by T cells in multiple sclerosis

1. 为了研究多发性硬化症（MS）患者的T细胞受体（TCR）库，我们引入了一种新的克隆型分析方法——单链构象多态性（SSCP）。通过该技术，我们分析了MS患者脑病变和外周血中的TCR库。(1)浸润到大脑中的克隆数量是适度限制的（50-100个/病变），尽管没有注意到对特定Vbeta基因的特殊偏好。(2)髓鞘碱性蛋白（MBP） 82-102或蛋白脂质蛋白（PLP） 95-116特异性T细胞在研究患者体内扩增和激活。(3)慢性炎症性脱髓鞘性多神经病变（CIDP）周围神经中的T细胞优先利用Vbeta11基因。这些结果表明，参与MS和CIDP发育的克隆数量有限，MBP和PLP是MS - 2的候选自身抗原。一般认为，自身免疫性脑原性T细胞的识别对其自身的脑原性表位具有高度特异性。然而，我们发现来自SJL/J小鼠的mbp89 -101特异性脑源性T细胞克隆也可以共同识别PLP136-150和PLP95-116。用丙氨酸替代类似物进行的实验表明，I-A^s结合残基与MBP89-101和PLP136-150相似。但TCR接触残留物似乎有所不同。因此，我们得出结论，一些自身免疫T细胞具有多反应性，可以有多组TCR接触位点。

1. To study the T cell receptor (TCR) repertoire in multiple sclerosis (MS), we have introduced a novel clonotype analysis method, single strand conformation polymorphism (SSCP). By using this technique, we analyzed the TCR repertoire in the brain lesions and peripheral blood of MS patients. The following points have emerged : (1) the number of clones infiltrated in the brains is moderately restricted (50-100/lesion), though no special preference for a particular Vbeta gene is noted. (2) myelin basic protein (MBP) 82-102 or proteolipid protein (PLP) 95-116-specific T cells are in vivo expanded and activated in the patients studied. (3) T cells in the peripheral nerves of chronic inflammatory demyelinating polyneuropathy (CIDP) preferentially utilize Vbeta11 gene. These results indicate that a limited number of clones are involved in the development of MS and CIDP,and MBP and PLP are candidate autoantigens for MS.2. It is generally believed that recognition by autoimmune encephalito genic T cells is highly specific for their own encephalito genic epitope. However, we have found that MBP89-101-specific encephalitogenic T cells clones derived from SJL/J mice can corecognize PLP136-150 and PLP95-116 as well. Experiments with alanin substitution analogues showed that I-A^s binding residues appeared to be shared by MBP89-101 and PLP136-150. But TCR contact residues seemed to be different. Thus, it has been concluded that some autoimmune T cells are polyreactive and can have multiple sets of TCR contact sites.