Therapeutic vaccination of active arthritis with a glycosylated collagen Type II peptide in complex with MHC class II molecules

In both collagen-induced arthritis (CIA) and rheumatoid arthritis, T cells recognize a galactosylated peptide from type II collagen (CII). In this study, we demonstrate that the CII259-273 peptide, galactosylated at lysine 264, in complex with A(q) molecules prevented development of CIA in mice and ameliorated chronic relapsing disease. In contrast, nonglycosylated C11259-273/A(q) complexes had no such effect. CIA dependent on other MHC class II molecules (A(r)/E-r) was also down-regulated, indicating a bystander vaccination effect. T cells could transfer the amelioration of CIA, showing that the protection is an active process. Thus, a complex between MHC class II molecules and a posttranslationally modified peptide offers a new possibility for treatment of chronically active autoimmune inflammation such as rheumatoid arthritis.