Specific treatment of autoimmunity with recombinant invariant chains in which CLIP is replaced by self-epitopes

The invariant chain (Ii) binds to newly synthesized MHC class If molecules with the CLIP region of Ii occupying the peptide-binding groove. Here we de monstrate that recombinant Ii proteins with the CLIP region replaced by ant igenic self-epitopes are highly efficient in activating and silencing speci fic T cells in vitro and in vivo. The Ii proteins require endogenous proces sing by antigen-presenting cells for efficient T cell activation. An Ii pro tein encompassing the epitope myelin basic protein amino acids 84-96 (Ii-MB P84-96) induced the model autoimmune disease experimental allergic encephal omyelitis (EAE) with a higher severity and earlier onset than the peptide. When applied in a tolerogenic manner, Ii-MBP84-96 abolished antigen-specifi c T cell proliferation and suppressed peptide-induced EAE more effectively than peptide alone. Importantly, Lv. administration of Ii proteins after EA E induction completely abrogated the disease, whereas peptides only margina lly suppressed disease symptoms. Ii fusion proteins are thus more efficient than peptide in modulating CD4(+) T cell-mediated autoimmunity, documentin g their superior qualities for therapeutic antigen delivery in vivo.