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

Frontiers in Immunology
Melanie D LeechStephen M Anderton

Abstract

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 (WT) 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 WT 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 WT 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 ...Continue Reading

Citations

Apr 10, 2013·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Rhoanne C McPherson, Stephen M Anderton
Sep 14, 2011·FEBS Letters·A SaxenaR S Liblau
Nov 21, 2015·Neurology. Neuroimmunology and Neuroinflammation·Sterling B OrtegaNitin J Karandikar

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Methods Mentioned

BETA
transgenic
ELISA
FACS
density gradient centrifugation
flow cytometry

Software Mentioned

Flowjo

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