Recognition of a high affinity MHC class I-restricted epitope of myelin oligodendrocyte glycoprotein by CD8+ T cells derived from autoantigen-deficient mice.

• Main Authors: Melanie D Leech, Antonio eCarrillo-Vico, Roland S. Liblau, Stephen M Anderton
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2011-05-01
• Series: Frontiers in Immunology
• Subjects: Multiple Sclerosis; T cells; tolerance; CD8+ T cells; Experimental autoimmune encephalomyelitis; myelin oligodendrocyte glycoprotein
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00017/full

CD4+ T cells have a well-defined pathogenic role in experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS), yet CD8+ T cells are commonly found in MS lesions. To determine whether immunological tolerance might impact differently on CD4+ versus CD8+ T cells, we studied T cell responses in mice genetically deficient for the central nervous system (CNS) autoantigen myelin oligodendrocyte glycoprotein (MOG) versus wild type C57BL/6 mice. We show that MOG-/- mice have enhanced sensitivity to immunization with the immunodominant peptide of MOG(35-55), as evidenced by increased expansion of both CD4+ and CD8+ T cell subsets. Most strikingly, CD8+ T cells from MOG-/- mice responded to a novel T cell epitope which binds to MHC class I with high affinity. Despite this, MOG-responsive CD8+ T cells sourced from either wild type or MOG-/- mice failed to initiate CNS inflammation upon transfer to MOG-sufficient mice. In our hands, this capacity was only found in CD4+ T cells. However, MOG-/- CD4+ cells did not show greater pathogenic activity than their wild type counterparts. Our data indicate that, in the presence of endogenous MOG, CD8+ T cells capable of responding to a MHC class I-restricted epitope that can be stably expressed are subject to rigorous control through central and/or peripheral tolerance.