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

Arthur A. Vandenbark, Roberto Meza-Romero, Gil Benedek, Shayne Andrew, Jianya Huan, Yuan K. Chou, Abigail C. Buenafe, Rony Dahan, Yoram Reiter, Jeffery L. Mooney, Halina Offner, Gregory G. Burrows

Research output: Contribution to journalArticle

28 Scopus citations

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 languageEnglish (US)
Pages (from-to)96-110
Number of pages15
JournalJournal of Autoimmunity
Volume40
Issue number1
DOIs
StatePublished - Feb 2013

Keywords

  • CD74
  • EAE
  • MIF
  • Partial MHC class II

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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