MHC class II derived recombinant T cell receptor ligands protect DBA/1LacJ mice from collagen-induced arthritis

Jianya Huan, Laurie J. Kaler, Jeffery L. Mooney, Sandhya Subramanian, Corwyn Hopke, Arthur Vandenbark, Edward F. Rosloniec, Gregory G. Burrows, Halina Offner

Research output: Contribution to journalArticle

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Abstract

We previously demonstrated the therapeutic effects of MHC class II derived recombinant T cell receptor ligands (RTL), singlechain two domain complexes of the α1 and β1 domains of MHC class II molecules genetically linked with an immunodominant peptide, in experimental autoimmune encephalomyelitis. In the current study, we produced a monomeric murine I-Aq-derived RTL construct covalently linked with bovine collagen type II peptide (bCII257-270) suitable for use in DBA/1LacJ mice that develop collagen-induced arthritis (CIA), an animal model of human rheumatoid arthritis, after immunization with bCII protein in CFA. In this study, we demonstrate that the I-A q-derived RTLs reduced the incidence of the disease, suppressed the clinical and histological signs of CIA and induced long-term modulation of T cells specific for arthritogenic Ags. Our results showed that the I-A q/bCII257-270 molecule could systemically reduce proinflammatory IL-17 and IFN-γ production and significantly increase anti-inflammatory IL-10, IL-13, and FoxP3 gene expression in splenocytes. Moreover, I-A q/bCII257-270 molecule could also selectively inhibit IL-1β, IL-6, and IL-23 expression in local joint tissue. This is the first report demonstrating effective prevention of joint inflammation and clinical signs of CIA with an I-Aq-derived RTL, thus supporting the possible clinical use of this approach for treating rheumatoid arthritis in humans.

Original languageEnglish (US)
Pages (from-to)1249-1257
Number of pages9
JournalJournal of Immunology
Volume180
Issue number2
StatePublished - Jan 15 2008

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Inbred DBA Mouse
Experimental Arthritis
T-Cell Antigen Receptor
Ligands
Rheumatoid Arthritis
Joints
Interleukin-23
Peptides
Interleukin-13
Collagen Type II
Autoimmune Experimental Encephalomyelitis
Interleukin-17
Therapeutic Uses
Interleukin-1
Interleukin-10
Immunization
Interleukin-6
Anti-Inflammatory Agents
Animal Models
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

MHC class II derived recombinant T cell receptor ligands protect DBA/1LacJ mice from collagen-induced arthritis. / Huan, Jianya; Kaler, Laurie J.; Mooney, Jeffery L.; Subramanian, Sandhya; Hopke, Corwyn; Vandenbark, Arthur; Rosloniec, Edward F.; Burrows, Gregory G.; Offner, Halina.

In: Journal of Immunology, Vol. 180, No. 2, 15.01.2008, p. 1249-1257.

Research output: Contribution to journalArticle

Huan, J, Kaler, LJ, Mooney, JL, Subramanian, S, Hopke, C, Vandenbark, A, Rosloniec, EF, Burrows, GG & Offner, H 2008, 'MHC class II derived recombinant T cell receptor ligands protect DBA/1LacJ mice from collagen-induced arthritis', Journal of Immunology, vol. 180, no. 2, pp. 1249-1257.
Huan, Jianya ; Kaler, Laurie J. ; Mooney, Jeffery L. ; Subramanian, Sandhya ; Hopke, Corwyn ; Vandenbark, Arthur ; Rosloniec, Edward F. ; Burrows, Gregory G. ; Offner, Halina. / MHC class II derived recombinant T cell receptor ligands protect DBA/1LacJ mice from collagen-induced arthritis. In: Journal of Immunology. 2008 ; Vol. 180, No. 2. pp. 1249-1257.
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