Vol.19 No.4

Original Article

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

Authors

Ei Wakamatsu1 , Isao Matsumoto1 , Yohei Yoshiga1 , Taichi Hayashi1 , Daisuke Goto1 , Satoshi Ito1 , Takayuki Sumida1

  • 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
Received:

4 March 2009

Accepted:

2 April 2009

Published online:

12 May 2009

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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.

Key words

Altered peptide ligand - Antagonist - Type II collagen-induced arthritis - T cells