A MYELIN OLIGODENDROCYTE GLYCOPROTEIN PEPTIDE INDUCES TYPICAL CHRONIC EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN H-2(B) MICE - FINE SPECIFICITY AND T-CELL RECEPTOR V-BETA EXPRESSION OF ENCEPHALITOGENIC T-CELLS
A MYELIN OLIGODENDROCYTE GLYCOPROTEIN PEPTIDE INDUCES TYPICAL CHRONIC EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN H-2(B) MICE - FINE SPECIFICITY AND T-CELL RECEPTOR V-BETA EXPRESSION OF ENCEPHALITOGENIC T-CELLS
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DOI：
10.1002/eji.1830250723
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发表时间：
1995-07-01
影响因子：
5.4
通讯作者：
BENNUN, A
中科院分区：
文献类型：
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作者：
MENDEL, I;DEROSBO, NK;BENNUN, A
最近在多发性硬化症 (MS) 患者中观察到对髓磷脂少突胶质细胞糖蛋白 (MOG) 的显着反应。为了研究 T 细胞对 MOG 反应在 MS 中可能的致病作用，我们研究了 MOG 的脑炎潜力。将代表预测 T 细胞表位的合成 MOG 肽 pMOG 1-21、35-55、67-87、104-117 和 202-218 注射到 C57BL/6J 和 C3H.SW (H-2(b)) 小鼠中。小鼠对 pMOG 1-21、pMOG 35-55 和 pMOG 104-117 产生显着的特异性 T 细胞反应。然而，pMOG 35-55 是唯一可以引起神经损伤的 MOG 肽。这种高度可重复的疾病是慢性的，具有上行麻痹和神经病理学特征，与髓磷脂碱性蛋白或蛋白脂质蛋白诱导的实验性自身免疫性脑脊髓炎（EAE）中观察到的情况相当，但在 H-2(b) 小鼠中，该疾病始终没有缓解。这些特征与我们最近在患有 pMOG 35-55 诱导疾病的 PL (H-2(u)) 小鼠中观察到的特征明显不同。在 PL 小鼠中，pMOG 35-55 诱导非典型慢性复发性 EAE，其表达和进展是不可预测的。因此，在不同的小鼠品系中，相同的MOG肽可以诱导以上行麻痹为特征的典型EAE，或具有不可预测的临床症状的非典型EAE。来自 H-2(b) 小鼠的 pMOG 35-55 特异性 T 细胞识别 MOG 分子的氨基酸 40-55 内的表位，并且 pMOG 40-55 反应性 T 细胞系在转移到同基因受体中后会引起脑炎。致脑炎 pMOG 35-55 反应性 C57BL/6J T 细胞系表达 V beta 1、V beta 6、V beta 8、V beta 14 和 V beta 15 基因片段，pMOG 35-55 反应性 C3H.SW T 细胞系表达 V beta 1、V beta 2、V beta 6、V beta 8、V beta 10、V beta 14 和 V beta 15个基因片段。然而，在这两种小鼠品系中，V beta 8 基因产物的利用占主导地位（40-43%）。 pMOG 35-55 高度可重复的致脑炎活性强烈表明 T 细胞对 MS 中 MOG 的反应性具有致病作用，并支持 MOG 也可能是该疾病的主要靶抗原的可能性。
A predominant response to myelin oligodendrocyte glycoprotein (MOG) was recently observed in patients with multiple sclerosis (MS). To study the possible pathogenic role of T cell response to MOG in MS, we have investigated the encephalitogenic potential of MOG. Synthetic MOG peptides, pMOG 1-21, 35-55, 67-87, 104-117 and 202-218, representing predicted T cell epitopes, were injected into C57BL/6J and C3H.SW (H-2(b)) mice. The mice developed significant specific T cell responses to pMOG 1-21, pMOG 35-55 and pMOG 104-117. However, pMOG 35-55 was the only MOG peptide which could induce neurological impairment. The highly reproducible disease was chronic, with ascending paralysis and neuropathology comparable with those observed in experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein or proteolipid protein, except that in H-2(b) mice the disease was consistently non-remitting. These features differ markedly from those which we recently observed in PL (H-2(u)) mice with pMOG 35-55-induced disease. In PL mice, pMOG 35-55-induces atypical chronic relapsing EAE, the expression and progression of which are unpredictable. Hence, in different mouse strains, the same MOG peptide can induce typical EAE characterized by ascending paralysis, or atypical EAE with unpredictable clinical signs. pMOG 35-55-specific T cells from H-2(b) mice recognized an epitope within amino acids 40-55 of the MOG molecule, and pMOG 40-55-reactive T cell lines were encephalitogenic upon transfer into syngeneic recipients. The encephalitogenic pMOG 35-55-reactive C57BL/6J T cell lines expressed V beta 1, V beta 6, V beta 8, V beta 14 and V beta 15 gene segments, and the pMOG 35-55-reactive C3H.SW T cell lines expressed V beta 1, V beta 2, V beta 6, V beta 8, V beta 10, V beta 14, and V beta 15 gene segments. However, in both mouse strains, the utilization of the V beta 8 gene product was predominant (40-43 %). The highly reproducible encephalitogenic activity of pMOG 35-55 strongly suggests a pathogenic role for T cell reactivity to MOG in MS and supports the possibility that MOG may also be a primary target antigen in the disease.