We employed a fusion between αDCIR2 antibodies and the highly encephalitogenic peptide 139–151 of myelin-derived proteolipid protein (PLP139–151), to target CD11c +CD8- DCs with a DEC-205−DCIR2+ phenotype in vivo, and to substantially improve clinical symptoms in the PLP139–151-induced model of experimental autoimmune encephalomyelitis (EAE). This evidence concerns the gene ITGAX and experimental autoimmune encephalomyelitis.