pH-Dependent Interdomain Tethers of CD1b Regulate Its Antigen Capture
- 作者：Miguel Relloso ; Tan-Yun Cheng ; Jin S. Im ; Emilio Parisini ; Carme Roura-Mir ; Charles DeBono ; Dirk M. Zajonc ; Leonel F. Murga ; Mary Jo Ondrechen ; Ian A. Wilson ; Steven A. Porcelli ; D. Branch Moody
- 关键词：MOLIMMUNO
- 刊名：Immunity
- 出版年：2008
- 期刊代码：40_10747613
- 类别：imm
- 出版时间：13 June 2008
- 卷：28
- 期：6
- 页码：774-786
- 文件大小：1042 K
摘要
As CD1 proteins recycle between the cell surface and endosomes, they show altered receptiveness to lipid antigen loading. We hypothesized that changes in proton concentration encountered within distinct endosomal compartments influence the charge state of residues near the entrance to the CD1 groove and thereby control antigen loading. Molecular dynamic models identified flexible areas of the CD1b heavy chain in the superior and lateral walls of the A′ pocket. In these same areas, residues that carry charge in a pH-dependent manner (D60, E62) were found to tether the rigid ![]()
src="http://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">1 helix to flexible areas of the ![]()
src="http://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">2 helix and the 50-60 loop. After disruption of these tethers with acid pH or mutation, we observed increased association and dissociation of lipids with CD1b and preferential presentation of antigens with bulky lipid tails. We propose that ionic tethers act as molecular switches that respond to pH fluxes during endosomal recycling and regulate the conformation of the CD1 heavy chain to control the size and rate of antigens captured.