Abstract
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.
Original language | English (US) |
---|---|
Pages (from-to) | 96-110 |
Number of pages | 15 |
Journal | Journal of Autoimmunity |
Volume | 40 |
Issue number | 1 |
DOIs | |
State | Published - Feb 2013 |
Keywords
- CD74
- EAE
- MIF
- Partial MHC class II
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology