کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3367867 | 1592308 | 2013 | 15 صفحه PDF | دانلود رایگان |
Treatment with partial (p)MHC class II-β1α1 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-α1/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.
► Partial MHC class II constructs bind and downregulate CD74 on monocytes.
► Novel Partial MHC receptor on monocytes includes CD74, MHC class II and surface histones.
► Ligation of CD74 involves the HLA-DR-α1 domain and blocks MIF activity.
► Partial MHC/peptide treatment of EAE involves both specific and bystander suppression.
Journal: Journal of Autoimmunity - Volume 40, February 2013, Pages 96–110