Butyrophilin, a milk protein, modulates the encephalitogenic T cell response to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) induced by sensitization wi th myelin oligodendrocyte glycoprotein (MOG) is a T cell-dependent autoimmu ne disease that reproduces the inflammatory demyelinating pathology of mult iple sclerosis. We report that an encephalitogenic T cell response to MOG c an be either induced or alternatively suppressed as a consequence of immuno logical cross-reactivity, or "molecular mimicry" with the extracellular IgV -like domain of the milk protein butyrophilin (BTN), In the Dark Agouti rat , active immunization with native BTN triggers an inflammatory response in the CNS characterized by the formation of scattered meningeal and perivascu lar infiltrates of T cells and macrophages, We demonstrate that this pathol ogy is mediated by a MHC class II-restricted T cell response that cross-rea cts with the MOG peptide sequence 76-87, IGEGKVALRIQN (identities underline d), Conversely, molecular mimicry with BTN can be exploited to suppress dis ease activity in MOG-induced EAE, We demonstrate that not only is EAE media ted by the adoptive transfer of MDG(74-90) T cell lines markedly ameliorate d by i.v. treatment with the homologous BTN peptide, BTN74-90, but that thi s protective effect is also seen in actively induced disease following tran smucosal (intranasal) administration of the peptide. These results identify a mechanism by which the consumption of milk products may modulate the pat hogenic autoimmune response to MOG.