Abstract: Methods are disclosed for treating or inhibiting an autoimmune disease in a subject. In some embodiments, the disclosed methods include administering to the subject a therapeutically effective amount of one or more Major Histocompatibility Complex (MHC) molecules including covalently linked first, second and third domains; wherein the first domain is an MHC class II ?1 domain and the second domain is an MHC class II ?1 domain, wherein the amino terminus of the ?1 domain is covalently linked to the carboxy terminus of the ?1 domain; or wherein the first domain is an MHC class I ?1 domain and the second domain is an MHC class I ?2 domain, wherein the amino terminus of the ?2 domain is covalently linked to the carboxy terminus of the ?1 domain; and wherein the third domain is covalently linked to the first domain and comprises an antigen associated with the autoimmune disorder.