Altered peptide ligands regulate type II collagen-induced arthritis in mice.
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.
Wakamatsu
Ei
E
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.
Matsumoto
Isao
I
Yoshiga
Yohei
Y
Hayashi
Taichi
T
Goto
Daisuke
D
Ito
Satoshi
S
Sumida
Takayuki
T
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D002478:Cells, Cultured; D024043:Collagen Type II / Q000378:metabolism / Q000494:pharmacology*; D020381:Interleukin-17 / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008811:Mice, Inbred DBA; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D024043:Collagen Type II; D020381:Interleukin-17; D008024:Ligands; D010446:Peptide Fragments