|Title:||Arginines in the Cdr of Anti-Dsdna Autoantibodies Facilitate Cell Internalization Via Electrostatic Interactions||Authors:||SONG, YING-CHYI
HUANG, JASON C
|Keywords:||Arginine-rich peptides;Electrostatic interactions;Internalization;Systemic lupus erythematosus||Issue Date:||2008||Journal Volume:||v.38||Journal Issue:||n.11||Start page/Pages:||3178-3190||Source:||EUROPEAN JOURNAL OF IMMUNOLOGY||Abstract:||
Internalization 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.
|Appears in Collections:||分子醫學研究所|
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