A peptide-based tolerizing vaccine against autoimmune arthritis directly interacting with antigen-specific T cells

A longstanding goal has been to find an antigen-specific preventive therapy, i.e., a vaccine, for autoimmune diseases. Major hindrances have so far been to select natural regulatory antigen targets and side-effects induced by clustering the T cell receptor (TCR) or activating the costimulatory signals. Here we show that the administration of a mouse major histocompatibility complex class II protein binding a unique galactosylated collagen type II (COL2) peptide (Aq-galCOL2) directly interacts with the antigen specific TCR, and expands peripheral regulatory T cells, displaying a potent dominant suppressive effect and protection of collagen induced arthritis. The therapeutic effect is dominant and tissue specific as it is possible to transfer the effect with induced regulatory T cells and downregulate autoimmune arthritis induced by other antigens than COL2 or by passive transfer of antibodies. Thus, the here described tolerogenic approach may be a promising dominant antigen-specific therapy for RA, and in principle, for autoimmune diseases in general.