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Altered peptide ligands regulate type II collagen-induced arthritis in mice

  • Original Article
  • Published:
Modern Rheumatology

Abstract

We reported that peripheral blood mononuclear cells from HLA-DRB1*0101 Japanese patients with rheumatoid arthritis (RA) were highly reactive to 256–271 peptide of type II collagen (CII). Similar to RA, T cells reactive to CII (AA256–271) play a crucial role in the generation of arthritis in CII-induced arthritis mouse (I-Aq). In the present study, we regulated the CII reactivity of T cells from CIA mouse with I-Aq by altered peptide ligand (APL). Eight different APLs were designed and screened for their antagonistic activity using CII reactive cytokine production assay. Four APLs of CII 256–271 exhibited antagonistic activity in CII-reactive T cells. Moreover, intraperitoneally injected APL-5 (G262A) significantly suppressed CII-induced arthritis in mice, whereas the other three APLs did not. Compared with the control, APL-5 suppressed interleukin (IL)-17 production by T cells from CII-induced arthritis mice. These results suggest that CII APL is a potentially suitable therapeutic strategy for the control of RA.

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Acknowledgment

This work was supported in part by a Research Grant from the Ministry of Health, Labor, and Welfare, and the Research Grant from the Ministry of Education, Culture, Sports, Science, and Technology.

Conflict of interest statement

All of the authors confirm that they have no conflicts of interest with regard to this work.

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Authors and Affiliations

  1. Division of Clinical Immunology, Doctoral Programs in Medical Sciences, Major of Advanced Biomedical Applications, Graduate School Comprehensive Human Science, University of Tsukuba, 1-1-1 Tenodai, Tsukuba, Ibaraki, 305-8575, Japan

    Ei Wakamatsu, Isao Matsumoto, Yohei Yoshiga, Taichi Hayashi, Daisuke Goto, Satoshi Ito & Takayuki Sumida

Authors
  1. Ei Wakamatsu
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  2. Isao Matsumoto
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  3. Yohei Yoshiga
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  4. Taichi Hayashi
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  5. Daisuke Goto
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  6. Satoshi Ito
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  7. Takayuki Sumida
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Corresponding author

Correspondence to Takayuki Sumida.

Additional information

E. Wakamatsu is a research fellow of the Japan Society for the Promotion of Science.

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Wakamatsu, E., Matsumoto, I., Yoshiga, Y. et al. Altered peptide ligands regulate type II collagen-induced arthritis in mice. Mod Rheumatol 19, 366–371 (2009). https://doi.org/10.1007/s10165-009-0174-0

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  • DOI: https://doi.org/10.1007/s10165-009-0174-0

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