Zisman E, Brautbar C, Sela M, Abramsky O, Battat S, Kirshner S L, Katz-Levy Y, Dayan M, Mozes E
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Hum Immunol. 1995 Nov;44(3):121-30. doi: 10.1016/0198-8859(95)00094-1.
MG is an autoimmune disease in which T cells specific to T-cell epitopes of the human acetylcholine receptor play a role. We have identified two peptides, p195-212 and p259-271, of the human acetylcholine receptor alpha-subunit, to which PBLs of MG patients responded by proliferation. Nevertheless, proliferation assays are relatively complicated to perform and might be affected by medications taken by the patients. Therefore, we tested the possibility of using a different assay to determine recognition of these peptides by MG patients. Thus, we performed a direct binding assay using biotinylated peptides and APCs from peripheral blood of MG patients and healthy controls. With this assay we detected the binding of the two peptides to the surface of intact APCs of both MG patients and control donors. Moreover, the presentation of peptide p259-271 by individuals with MG was significantly higher than that observed in healthy subjects. The peptides were specifically bound to HLA class II determinants on the APCs, as shown by inhibition with antibodies to the HLA class II haplotypes of the individuals investigated. Moreover, the binding of these peptides was in correlation with their ability to induce specific proliferative responses of peripheral blood T cells of these patients. The ability to screen for potentially pathogenic epitopes in each patient is of importance for the future design of specific inhibitory analogues that might be used to treat MG.
重症肌无力（MG）是一种自身免疫性疾病，其中针对人类乙酰胆碱受体T细胞表位的T细胞发挥作用。我们已经鉴定出人类乙酰胆碱受体α亚基的两种肽段，即p195 - 212和p259 - 271，重症肌无力患者的外周血淋巴细胞（PBLs）对其有增殖反应。然而，增殖试验操作相对复杂，且可能受患者所服用药物的影响。因此，我们测试了使用不同检测方法来确定重症肌无力患者对这些肽段的识别情况的可能性。于是，我们使用生物素化肽段和来自重症肌无力患者及健康对照者外周血的抗原呈递细胞（APCs）进行了直接结合试验。通过该试验，我们检测到这两种肽段与重症肌无力患者和对照供者完整APCs表面的结合。此外，重症肌无力患者对肽段p259 - 271的呈递显著高于健康受试者。如用针对所研究个体的HLA - II类单倍型的抗体进行抑制试验所示，这些肽段特异性结合于APCs上的HLA - II类决定簇。而且，这些肽段的结合与其诱导这些患者外周血T细胞特异性增殖反应的能力相关。对每位患者筛选潜在致病表位的能力对于未来设计可能用于治疗重症肌无力的特异性抑制类似物至关重要。
