T Cells of Multiple Sclerosis Patients Target a Common Environmental Peptide that Causes Encephalitis in Mice1

Multiple sclerosis (MS) is a chronic autoimmune disease triggered by unknown environmental factors in genetically susceptible hosts. MS risk was linked to high rates of cow milk protein (CMP) consumption, reminiscent of a similar association in autoim-mune diabetes. A recent rodent study showed that immune responses to the CMP, butyrophilin, can lead to encephalitis through antigenic mimicry with myelin oligodendrocyte glycoprotein. In this study, we show abnormal T cell immunity to several other CMPs in MS patients comparable to that in diabetics. Limited epitope mapping with the milk protein BSA identified one specific epitope, BSA193, which was targeted by most MS but not diabetes patients. BSA193 was encephalitogenic in SJL/J mice subjected to a standard protocol for the induction of experimental autoimmune encephalitis. These data extend the possible, immunological basis for the association of MS risk, CMP, and CNS autoimmunity. To pinpoint the same peptide, BSA193, in encephalitis-prone humans and rodents may imply a common endogenous ligand, targeted through antigenic mimicry. The Journal of Immunology, 2001, 166: 4751–4756. M ultiple sclerosis (MS)4 is a chronic autoimmune dis-ease of genetically susceptible hosts (1). AutoreactiveT cells target constituents of myelin and oligodendro-cytes for destruction, once a breach of the blood-brain barrier al-lows invasion by monocytes, dendritic cells, and effector T lym-phocytes (2). MS has much in common with autoimmune type 1 diabete