These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Activation and control of pathogenic T cells in OSP/claudin-11-induced EAE in SJL/J mice are dominated by their focused recognition of a single epitopic residue (OSP58M).
    Author: Kaushansky N, Eisenstein M, Oved JH, Ben-Nun A.
    Journal: Int Immunol; 2008 Nov; 20(11):1439-49. PubMed ID: 18801757.
    Abstract:
    Oligodendrocyte-specific protein (OSP)/claudin-11 has been recently implicated in multiple sclerosis pathophysiology. Yet, the pathogenic autoimmunity against OSP has been poorly investigated. We previously showed that OSP-induced experimental autoimmune encephalomyelitis (EAE) and optic neuritis in SJL/J mice are primarily associated with CD4+ T cells reactive against OSP55-80. Dissecting the fine epitope specificity to the level of epitopic residues recognized by OSP-specific encephalitogenic T cells revealed their focused recognition of OSP58M. Accordingly, OSP58M predicted by computer modeling to be a major TCR contact residue shared by the three nonameric core epitopes within OSP55-80, albeit at different MHC-II pockets, was experimentally determined as the primary TCR contact residue crucial for activation and control of encephalitogenic T cells reactive against OSP55-80 or against recombinant OSP. Ala substitution of OSP58M impaired the functional TCR recognition/activation of pathogenic OSP-reactive T cells. Accordingly, the non-stimulatory/non-encephalitogenic pOSP55-58A-66 analogue not only treated EAE induced by pOSP55-80 but also effectively reversed EAE induced by whole OSP. Thus, the selection/activation and control of OSP-pathogenic T cells in H-2(s) mice appeared to be dominated by their predetermined focused recognition of OSP58M. Such a focused recognition by OSP-pathogenic T cells, despite their extensive TCR heterogeneity (Kaushansky, N., Zhong, M. C., Kerlero de Rosbo, N., Hoeftberger, R., Lassmann, H. and Ben-Nun, A. 2006. Epitope specificity of autoreactive T and B cells associated with experimental autoimmune encephalomyelitis and optic neuritis induced by oligodendrocyte-specific protein in SJL/J mice. J. Immunol. 177:7364), may impact profoundly on peripheral self-tolerance to OSP and on altered peptide ligand-mediated immune-specific modulation of the recently described OSP-related autoimmune pathogenesis.
    [Abstract] [Full Text] [Related] [New Search]