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

Nat Immunol. 2013 Mar;14(3):254-61. doi: 10.1038/ni.2513. Epub 2013 Jan 6.

Abstract

Myelin presentation to T cells in the central nervous system (CNS) sustains inflammation in multiple sclerosis (MS). CD4(+) and CD8(+) T cells contribute to MS, but only cells that present myelin to CD4(+) T cells have been identified. We show that MHC class I-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(+) T cells. Tip-DCs activated naive and effector CD8(+) T cells ex vivo, and naive MBP-specific CD8(+) T cells were activated in the CNS during CD4(+) T cell-induced EAE. These results demonstrate that CD4(+) T cell-mediated CNS autoimmunity leads to determinant spreading to myelin-specific CD8(+) T cells that can directly recognize oligodendrocytes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen Presentation
  • Autoimmunity / immunology
  • CD11c Antigen / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Central Nervous System / immunology
  • Cross-Priming*
  • Dendritic Cells / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Epitopes / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C3H
  • Mice, Transgenic
  • Monocytes / cytology
  • Monocytes / metabolism
  • Multiple Sclerosis / immunology
  • Myelin Basic Protein / immunology*
  • Oligodendroglia / immunology

Substances

  • CD11c Antigen
  • Epitopes
  • Myelin Basic Protein