Advanced SearchSearch Tips
Induction of tolerance against the arthritogenic antigen with type-II collagen peptide-linked soluble MHC class II molecules
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : BMB Reports
  • Volume 49, Issue 6,  2016, pp.331-336
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2016.49.6.207
 Title & Authors
Induction of tolerance against the arthritogenic antigen with type-II collagen peptide-linked soluble MHC class II molecules
Park, Yoon-Kyung; Jung, Sundo; Park, Se-Ho;
  PDF(new window)
In murine collagen-induced arthritis (CIA), self-reactive T cells can recognize peptide antigens derived from type-II collagen (CII). Activation of T cells is an important mediator of autoimmune diseases. Thus, T cells have become a focal point of study to treat autoimmune diseases. In this study, we evaluated the efficacy of recombinant MHC class II molecules in the regulation of antigen-specific T cells by using a self peptide derived from CII (CII260-274; IAGFKGEQGPKGEPG) linked to mouseI-Aq in a murine CIA model. We found that recombinant I-Aq/CII260-274 molecules could be recognized by CII-specific T cells and inhibit the same T cells in vitro. Furthermore, the development of CIA in mice was successfully prevented by in vivo injection of recombinant I-Aq/CII260-274 molecules. Thus, treatment with recombinant soluble MHC class II molecules in complex with an immunodominant self-peptide might offer a potential therapeutic for chronic inflammation in autoimmune disease such as rheumatoid arthritis.
Collagen-induced arthritis;Immunotherapy;Rheumatoid arthriti;Recombinant MHC II;Type-II collagen;
 Cited by
Imboden JB (2009) The immunopathogenesis of rheumatoid arthritis. Annu Rev Pathol 4, 417-434 crossref(new window)

Firestein GS (2004) The T cell cometh: interplay between adaptive immunity and cytokine networks in rheumatoid arthritis. J Clin Invest 114, 471-474 crossref(new window)

Courtenay JS, Dallman MJ, Dayan AD, Martin A and Mosedale B (1980) Immunisation against heterologous type II collagen induces arthritis in mice. Nature 283, 666-668 crossref(new window)

Zanelli E, Gonzalez-Gay MA and David CS (1995) Could HLA-DRB1 be the protective locus in rheumatoid arthritis? Immunol Today 16, 274-278 crossref(new window)

Trentham DE, Townes AS and Kang AH (1977) Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med 146, 857-868 crossref(new window)

Mauri C, Williams RO, Walmsley M and Feldmann M (1996) Relationship between Th1/Th2 cytokine patterns and the arthritogenic response in collagen-induced arthritis. Eur J Immunol 26, 1511-1518 crossref(new window)

Ortmann RA and Shevach EM (2001) Susceptibility to collagen-induced arthritis: cytokine-mediated regulation. Clin Immunol 98, 109-118 crossref(new window)

Miossec P and van den Berg W (1997) Th1/Th2 cytokine balance in arthritis. Arthritis Rheum 40, 2105-2115 crossref(new window)

Burrows GG (2005) Systemic immunomodulation of autoimmune disease using MHC-derived recombinant TCR ligands. Curr Drug Targets Inflamm Allergy 4, 185-193 crossref(new window)

Quill H and Schwartz RH (1987) Stimulation of normal inducer T cell clones with antigen presented by purified Ia molecules in planar lipid membranes: specific induction of a long-lived state of proliferative nonresponsiveness. J Immunol 138, 3704-3712

Schwartz RH (1996) Models of T cell anergy: is there a common molecular mechanism? J Exp Med 184, 1-8 crossref(new window)

Appel H, Seth NP, Gauthier L and Wucherpfennig KW (2001) Anergy induction by dimeric TCR ligands. J Immunol 166, 5279-5285 crossref(new window)

Smith-Garvin JE, Koretzky GA and Jordan MS (2009) T cell activation. Annu Rev Immunol 27, 591-619 crossref(new window)

DeFord-Watts LM, Dougall DS, Belkaya S et al (2011) The CD3 zeta subunit contains a phosphoinositide-binding motif that is required for the stable accumulation of TCR-CD3 complex at the immunological synapse. J Immunol 186, 6839-6847 crossref(new window)

Appleman LJ and Boussiotis VA (2003) T cell anergy and costimulation. Immunol Rev 192, 161-180 crossref(new window)

Rhode PR, Burkhardt M, Jiao J, Siddiqui AH, Huang GP and Wong HC (1996) Single-chain MHC class II molecules induce T cell activation and apoptosis. J Immunol 157, 4885-4891

Nag B, Kendrick T, Arimilli S, Yu SC and Sriram S (1996) Soluble MHC II-peptide complexes induce antigen-specific apoptosis in T cells. Cell Immunol 170, 25-33 crossref(new window)

Mu CX, Liu GL, Tian H, Li YC and Huang YL (2014) [Effect of Tetramethyl pyrazine on serum levels of IL-1beta, IL-6, and IL-2, and NO and PGE2 in the synovial fluid of CIA rats: an experimental research]. Zhongguo Zhong Xi Yi Jie He Za Zhi 34, 214-217

Zhang Y, Ren G, Guo M et al (2013) Synergistic effects of interleukin-1beta and interleukin-17A antibodies on collagen-induced arthritis mouse model. Int Immunopharmacol 15, 199-205 crossref(new window)

Nakajima A, Seroogy CM, Sandora MR et al (2001) Antigen-specific T cell-mediated gene therapy in collagen-induced arthritis. J Clin Invest 107, 1293-1301 crossref(new window)

Morita Y, Yang J, Gupta R et al (2001) Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced arthritis. J Clin Invest 107, 1275-1284 crossref(new window)

Savage P, Millrain M, Dimakou S, Stebbing J and Dyson J (2007) Expansion of CD8+ cytotoxic T cells in vitro and in vivo using MHC class I tetramers. Tumour Biol 28, 70-76 crossref(new window)

Huan J, Kaler LJ, Mooney JL et al (2008) MHC class II derived recombinant T cell receptor ligands protect DBA/1LacJ mice from collagen-induced arthritis. J Immunol 180, 1249-1257 crossref(new window)

Mealey RH, Sharif A, Ellis SA, Littke MH, Leib SR and McGuire TC (2005) Early detection of dominant Env-specific and subdominant Gag-specific CD8+ lymphocytes in equine infectious anemia virus-infected horses using major histocompatibility complex class I/peptide tetrameric complexes. Virology 339, 110-126 crossref(new window)

Offner H, Sinha S, Wang C, Burrows GG and Vandenbark AA (2008) Recombinant T cell receptor ligands: immunomodulatory, neuroprotective and neuroregenerative effects suggest application as therapy for multiple sclerosis. Rev Neurosci 19, 327-339 crossref(new window)

Huan J, Subramanian S, Jones R et al (2004) Monomeric recombinant TCR ligand reduces relapse rate and severity of experimental autoimmune encephalomyelitis in SJL/J mice through cytokine switch. J Immunol 172, 4556-4566 crossref(new window)

Kotzin BL, Falta MT, Crawford F et al (2000) Use of soluble peptide-DR4 tetramers to detect synovial T cells specific for cartilage antigens in patients with rheumatoid arthritis. Proc Natl Acad Sci U S A 97, 291-296 crossref(new window)

Lovitch SB, Pu Z and Unanue ER (2006) Amino-terminal flanking residues determine the conformation of a peptide-class II MHC complex. J Immunol 176, 2958-2968 crossref(new window)

Ren D, Wang F, He X et al (2006) Construction of bioactive chimeric MHC class I tetramer by expression and purification of human-murine chimeric MHC heavy chain and beta(2)m as a fusion protein in Escherichia coli. Protein Expr Purif 50, 171-178 crossref(new window)

Brand DD, Latham KA and Rosloniec EF (2007) Collageninduced arthritis. Nat Protoc 2, 1269-1275 crossref(new window)

Park J, Bae EK, Lee C et al. (2014) Establishment and characterization of bortezomib-resistant U266 cell line: constitutive activation of NF-kappaB-mediated cell signals and/or alterations of ubiquitylation-related genes reduce bortezomib-induced apoptosis. BMB Rep 47, 274-279 crossref(new window)