生物素化
主要组织相容性复合体
抗原
表位
MHC II级
髓鞘碱性蛋白
MHC I级
生物
分子生物学
MHC限制
抗原提呈细胞
抗原呈递
T细胞
化学
生物化学
髓鞘
免疫系统
免疫学
神经科学
中枢神经系统
作者
Masha Fridkis‐Hareli,Dvora Teitelbaum,E Gurevich,Israel Pecht,Chaim Brautbar,Oh-Jung Kwon,Talma Brenner,Ruth Arnon,Michael Sela
标识
DOI:10.1073/pnas.91.11.4872
摘要
Copolymer 1 (Cop 1) is a synthetic basic random copolymer of amino acids that has been shown to be effective in suppression of experimental allergic encephalomyelitis and is being tested as a candidate drug for multiple sclerosis. It has been previously demonstrated that Cop 1 is immunologically cross-reactive with the autoantigen myelin basic protein (BP) and competitively inhibits the response to BP of T-cell lines and clones of different major histocompatibility complex (MHC) restrictions, of both mouse and human origin. In the present study we demonstrated the direct binding of Cop 1, using its biotinylated derivative, to MHC molecules on living antigen-presenting cells. Binding of biotinylated BP and peptide p84-102 (an immunodominant epitope of BP) was also demonstrated. Cop 1 and BP bound in a promiscuous manner to different types of antigen-presenting cells of various H-2 and HLA haplotypes. The specificity of the binding was confirmed by its inhibition with either the relevant anti-MHC class II antibodies or unlabeled analogs. Cop 1 exhibited the most extensive and fast binding to antigen-presenting cells. In addition, Cop 1 inhibited the binding of biotinylated derivatives of BP and of p84-102 to the MHC class II molecules and even displaced these antigens when already bound. Thus, these results suggest that Cop 1 indeed competes with BP for MHC binding and, thereby, inhibits T-cell responses to BP. The binding of Cop 1 to different DR alleles, probably because of its multiple MHC binding motifs, may indicate its potential as a broad-spectrum drug for multiple sclerosis.
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