分子醫學研究所SONG, YING-CHYIYING-CHYISONGSUN, GUANG-HUANGUANG-HUANSUNLEE, TAI-PINGTAI-PINGLEEHUANG, JASON CJASON CHUANGYU, CHIA-LICHIA-LIYU2009-12-182018-07-092009-12-182018-07-092008http://ntur.lib.ntu.edu.tw//handle/246246/174493Internalization of autoantibodies against double-stranded DNA (anti-dsDNA ) is crucial to the pathogenesis of systemic lupus erythematosus. Anti- dsDNA may bind to cell-surface targets in order to facilitate the subsequent cell penetration of the anti-dsDNA. in this study, we observed that the 9D7 monoclonal anti-dsDNA autoantibody (9D7 mAb) penetrates into Jurkat cells via a novel alternative pathway . Endocytosis inhibitors or a lipid-raft inhibitor did not significantly change the penetration of 9D7 mAb into the Jurkat cells. However, heparin sulfate, chondroitin sulfate B , decaarginine and chondroitinase ABC significantly suppressed the internalization and the 9D7 mAb inhibited the internalization of Tat-GFP. Moreover, the penetration of the 9D7 mAb was significantly reduced in proteoglycan- deficient cells (pgs A-745). Positively charged amino acids including arginine are commonly found in the CDR of the 9D7 mAb. Point mutations to the arginine residues in the CDR of the H chain of the recombinant 9D7 mAb significantly attenuated its DNA-binding and cell- penetration abilities. These findings indicate that cell penetration of anti-dsDNA is due to the electrostatic interactions of arginine residues in the CDR with the negatively charged sulfated polysaccharides on the cell surface.en-USArginine-rich peptidesElectrostatic interactionsInternalizationSystemic lupus erythematosus