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

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-A^q). In the present study, we regulated the CII reactivity of T cells from CIA mouse with I-A^q 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.

Keywords::

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