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

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• 作者：Arthur A. Vandenbark^a ; ^b ; ^c ; ^d ; ^e ; ¹ ; ^{vandenba@ohsu.edu} ; Roberto Meza-Romero^b ; ^c ; ¹ ; Gil Benedek^b ; ^c ; ^d ; ¹ ; Shayne Andrew^b ; ^c ; Jianya Huan^c ; Yuan K. Chou^c ; ^d ; Abigail C. Buenafe^c ; Rony Dahan^f ; Yoram Reiter^f ; Jeffery L. Mooney^c ; Halina Offner^b ; ^d ; ^g ; Gregory G. Burrows^c ; ^d ; ^h ; ⁱ
• 关键词：Partial MHC class II ; CD74 ; EAE ; MIF
• 刊名：Journal of Autoimmunity
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：40
• 期：Complete
• 页码：96-110
• 全文大小：1830 K

文摘

Treatment with partial (p)MHC class II-¦Â1¦Á1 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-¦Á1/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.