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 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

27 Citations (Scopus)

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

Fingerprint

Autoimmune Diseases
Monocytes
Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Macrophage Migration-Inhibitory Factors
Ligands
T-Cell Antigen Receptor
Histones
Antigens
Peptides
invariant chain

Keywords

  • CD74
  • EAE
  • MIF
  • Partial MHC class II

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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. / Vandenbark, Arthur; 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.

In: Journal of Autoimmunity, Vol. 40, No. 1, 02.2013, p. 96-110.

Research output: Contribution to journalArticle

Vandenbark, Arthur ; 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. / 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. In: Journal of Autoimmunity. 2013 ; Vol. 40, No. 1. pp. 96-110.
@article{c82fe7add2484f82a84837bc9a97bdb0,
title = "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",
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.",
keywords = "CD74, EAE, MIF, Partial MHC class II",
author = "Arthur Vandenbark and Roberto Meza-Romero and Gil Benedek and Shayne Andrew and Jianya Huan and Chou, {Yuan K.} and Buenafe, {Abigail C.} and Rony Dahan and Yoram Reiter and Mooney, {Jeffery L.} and Halina Offner and Burrows, {Gregory G.}",
year = "2013",
month = "2",
doi = "10.1016/j.jaut.2012.08.004",
language = "English (US)",
volume = "40",
pages = "96--110",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - A novel regulatory pathway for autoimmune disease

T2 - Binding of partial MHC class II constructs to monocytes reduces CD74 expression and induces both specific and bystander T-cell tolerance

AU - Vandenbark, Arthur

AU - Meza-Romero, Roberto

AU - Benedek, Gil

AU - Andrew, Shayne

AU - Huan, Jianya

AU - Chou, Yuan K.

AU - Buenafe, Abigail C.

AU - Dahan, Rony

AU - Reiter, Yoram

AU - Mooney, Jeffery L.

AU - Offner, Halina

AU - Burrows, Gregory G.

PY - 2013/2

Y1 - 2013/2

N2 - 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.

AB - 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.

KW - CD74

KW - EAE

KW - MIF

KW - Partial MHC class II

UR - http://www.scopus.com/inward/record.url?scp=84873719333&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873719333&partnerID=8YFLogxK

U2 - 10.1016/j.jaut.2012.08.004

DO - 10.1016/j.jaut.2012.08.004

M3 - Article

C2 - 23026773

AN - SCOPUS:84873719333

VL - 40

SP - 96

EP - 110

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

IS - 1

ER -