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Therapeutic Vaccination of Active Arthritis with a Glycosylated Collagen Type II Peptide in Complex with MHC Class II Molecules¹

Balik Dzhambazov^*, Kutty Selva Nandakumar^*, Jan Kihlberg, Lars Fugger, Rikard Holmdahl^2,* and Mikael Vestberg^*

^* Medical Inflammation Research, Lund University, Lund, Sweden; Department of Chemistry, Umeå University, Umeå, Sweden; and Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom

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 CII259–273/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.

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