Pelfrey C M, Trotter J L, Tranquill L R, McFarland H F
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
J Neuroimmunol. 1993 Jul;46(1-2):33-42. doi: 10.1016/0165-5728(93)90231-m.
Research into the pathogenesis of multiple sclerosis (MS) has focused on myelin antigens as potential targets of autoimmune attack. Proteolipid protein (PLP), which makes up more than 50% of central nervous system myelin, is a hydrophobic membrane protein with many properties that historically have made it difficult to study. The use of synthetic peptides based on the PLP sequence provides an alternative method for studying the immunological properties of PLP. Using peripheral blood lymphocytes from MS patients, long-term TCL established in the presence of PLP reacted weakly to PLP in proliferation assays; however, these same lines were much more reactive to synthetic peptides of PLP. Thus, we established short-term T cell lines (TCL) from the peripheral blood lymphocytes (PBL) of MS patients in the presence of five separate synthetic PLP peptides. In six out of seven MS patients, proliferative responses were elicited most often to PLP 40-60 compared to four other PLP peptides (PLP 89-106, 103-120, 125-143, and 139-154). Characterization of PLP 40-60-responsive TCL from a single MS patient, MS1, indicated that six out of seven TCL proliferating to the peptide also lysed PLP 40-60 pulsed autologous targets. All cytolytic PLP 40-60 TCL were CD4+ and MHC class II restricted and further analysis of MS1 TCL showed that the PLP 40-60 TCL were restricted by DR4 whereas the MBP TCL from MS1 were restricted by DR6. These findings suggest that difficulties in examining the immune response to PLP have been due to the poor response generated in vitro using the whole molecule and that the use of synthetic peptides may represent an alternative approach to the study of PLP. These results also suggest that MS PBL recognize several PLP peptides, with the predominant response to PLP 40-60. Since these cells phenotypically resemble T cells known to mediate experimental autoimmune encephalomyelitis, it is possible that they may play a role in the pathogenesis of MS.
对多发性硬化症（MS）发病机制的研究聚焦于髓磷脂抗原，将其作为自身免疫攻击的潜在靶点。蛋白脂质蛋白（PLP）占中枢神经系统髓磷脂的50%以上，是一种疏水性膜蛋白，其诸多特性使得历史上对它的研究颇具难度。基于PLP序列使用合成肽提供了一种研究PLP免疫特性的替代方法。使用MS患者的外周血淋巴细胞，在PLP存在的情况下建立的长期T细胞系（TCL）在增殖试验中对PLP反应较弱；然而，这些细胞系对PLP的合成肽反应更强。因此，我们在五种不同的合成PLP肽存在的情况下，从MS患者的外周血淋巴细胞（PBL）中建立了短期T细胞系（TCL）。在七名MS患者中的六名中，与其他四种PLP肽（PLP 89 - 106、103 - 120、125 - 143和139 - 154）相比，对PLP 40 - 60的增殖反应最为常见。对来自一名MS患者MS1的PLP 40 - 60反应性TCL的特性分析表明，在七种对该肽增殖的TCL中，有六种也裂解了用PLP 40 - 60脉冲处理的自体靶细胞。所有细胞溶解性PLP 40 - 60 TCL均为CD4 + 且受MHC II类分子限制，对MS1 TCL的进一步分析表明，PLP 40 - 60 TCL受DR4限制，而来自MSI的MBP TCL受DR6限制。这些发现表明，检测对PLP免疫反应存在困难是由于使用整个分子在体外产生的反应较差，而使用合成肽可能代表了一种研究PLP的替代方法。这些结果还表明，MS PBL识别几种PLP肽，对PLP 40 - 60的反应占主导。由于这些细胞在表型上类似于已知介导实验性自身免疫性脑脊髓炎的T细胞，它们有可能在MS的发病机制中发挥作用。
