A novel regulatory pathway for autoimmune disease: Binding of partial MHC class II constructs to monocytes reduces CD74 expression and induces both specific and bystander T-cell tolerance

作者：Vandenbark Arthur A^*; Meza Romero Roberto; Benedek Gil; Andrew Shayne; Huan Jianya; Chou Yuan K; Buenafe Abigail C; Dahan Rony; Reiter Yoram; Mooney Jeffery L; Offner Halina; Burrows Gregory G

来源：Journal of Autoimmunity, 2013, 40: 96-110.

DOI：10.1016/j.jaut.2012.08.004

• Partial MHC class II
• CD74
• EAE
• MIF

Treatment with partial (p)MHC class II-beta 1 alpha 1 constructs (also referred to as recombinant T-cell receptor ligands - RTL) linked to antigenic peptides can induce T-cell tolerance, inhibit recruitment of inflammatory cells and reverse autoimmune diseases. Here we demonstrate a novel regulatory pathway that involves RTL binding to CD11b(+) mononuclear cells through a receptor comprised of MHC class II invariant chain (CD74), cell-surface histones and MHC class II itself for treatment of experimental autoimmune encephalomyelitis (EAE). Binding of RTL constructs with CD74 involved a previously unrecognized MHC class II-alpha 1/CD74 interaction that inhibited CD74 expression, blocked activity of its ligand, macrophage migration inhibitory factor, and reduced EAE severity. These findings implicate binding of RTL constructs to CD74 as a key step in both antigen-driven and bystander T-cell tolerance important in treatment of inflammatory diseases. Published by Elsevier Ltd.

• 出版日期2013-2