Hill M, Moss P, Wordsworth P, Newsom-Davis J, Willcox N
Neurosciences Group, Institute of Molecular Medicine, The John Radcliffe Hospital, Headington, Oxford, UK.
J Neuroimmunol. 1999 Jun 1;97(1-2):146-53. doi: 10.1016/s0165-5728(99)00038-7.
The anti-rheumatoid drug D-penicillamine (D-pen) has a reactive sulfhydryl group capable of modifying self antigens, and can provoke typical autoantibody-mediated myasthenia gravis (MG), especially in DR1+ individuals. We have selected T cell clones from one such patient that were highly specific for D-pen but not its L-isomer or D-cysteine. Moreover, they were restricted to HLA-DR1, had a Th1 phenotype and used TCR V alpha4.1, V beta6.1. They responded well to blood mononuclear cells prepulsed with D-pen either in the absence of serum or after chloroquine treatment, but not to autologous D-pen-pulsed B cell lines. Thus, D-pen may directly couple to distinctive peptides resident in surface DR1 molecules on circulating macrophages or dendritic cells.
抗类风湿药物D-青霉胺（D-pen）具有一个能修饰自身抗原的反应性巯基，可引发典型的自身抗体介导的重症肌无力（MG），尤其是在DR1+个体中。我们从一名此类患者中筛选出了对D-青霉胺具有高度特异性，但对其L-异构体或D-半胱氨酸无特异性的T细胞克隆。此外，它们受限于HLA-DR1，具有Th1表型并使用TCR V alpha4.1、V beta6.1。在无血清或氯喹处理后，它们对预先用D-青霉胺脉冲处理的血液单核细胞反应良好，但对自体D-青霉胺脉冲处理的B细胞系无反应。因此，D-青霉胺可能直接与循环巨噬细胞或树突状细胞表面DR1分子上的独特肽段结合。
