MHC class I-restricted myelin epitopes are cross-presented by Tip-DCs that promote determinant spreading to [CD8.sup.+] T cells

Myelin presentation to T cells in the central nervous system (CNS) sustains inflammation in multiple sclerosis (MS). [CD4.sup.+] and [CD8.sup.+] T cells contribute to MS, but only cells that present myelin to [CD4.sup.+] T cells have been identified. We show that MHC class l-restricted myelin basic protein (MBP) was presented by oligodendrocytes and cross-presented by Tip-dendritic cells (DCs) during experimental autoimmune encephalomyelitis (EAE), an animal model of MS initiated by [CD4.sup.+] T cells. Tip-DCs activated naive and effector [CD8.sup.+] T cells ex vivo, and naive MBP-specific [CD8.sup.+] T cells were activated in the CNS during [CD4.sup.+] T cell-induced EAE. These results demonstrate that [CD4.sup.+] T cell-mediated CNS autoimmunity leads to determinant spreading to myelin-specific [CD8.sup.+] T cells that can directly recognize oligodendrocytes.