An MHC anchor-substituted analog of myelin oligodendrocyte glycoprotein 35-55 induces IFN-gamma and autoantibodies in the absence of experimental autoimmune encephalomyelitis and optic neuritis.

Abstract

Previous strategies to ameliorate experimental autoimmune encephalitis (EAE) include the treatment of autoreactive T cells with altered peptide ligands, which contain amino acid substitutions at TCR contact residues. We recently showed that a variant of myelin oligodendrocyte glycoprotein (MOG) 35-55 possessing low affinity for MHC (45D) induced anergy in MOG 35-55-specific T cells and reduced their encephalitogenicity upon adoptive transfer. Here we investigate the characteristics of the primary immune response to this MHC anchor-substituted peptide. Overall, we observed that immunization with 45D resulted in the production of IFN-gamma and anti-MOG 35-55 autoantibodies at levels similar to those of MOG 35-55-immunized mice with active EAE. However, no symptoms of clinical or histological EAE or overt histological optic neuritis were observed in 45D-immunized mice. Consistent with this finding, 45D-immunized mice did not exhibit CD4(+) infiltrates into the CNS. Therefore, MOG 35-55-specific precursors stimulated with a weak ligand (45D) mediate some EAE-associated effector functions but are unable to fully initiate the inflammatory process in the central nervous system that leads to clinical manifestation of EAE.

• Authors: Mandy L Ford, Brian D Evavold
• Journal: European journal of immunology (Eur J Immunol) Vol. 34 Issue 2 Pg. 388-97 (Feb 2004) ISSN: 0014-2980 [Print] Germany
• PMID: 14768043 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Autoantibodies
• Glycoproteins
• Histocompatibility Antigens
• Immunoglobulin G
• Interleukin-2
• Myelin-Oligodendrocyte Glycoprotein
• Peptide Fragments
• Peptides
• myelin oligodendrocyte glycoprotein (35-55)
• Interleukin-4
• Interferon-gamma

Topics

• Animals
• Autoantibodies (biosynthesis, immunology)
• Brain (immunology, pathology)
• CD4-Positive T-Lymphocytes (cytology, immunology)
• Cell Division
• Encephalomyelitis, Autoimmune, Experimental (immunology, pathology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Glycoproteins (immunology)
• Histocompatibility Antigens (immunology)
• Immunoglobulin G (blood)
• Interferon-gamma (biosynthesis, immunology, metabolism)
• Interleukin-2 (immunology, metabolism)
• Interleukin-4 (immunology, metabolism)
• Mice
• Mice, Inbred C57BL
• Myelin-Oligodendrocyte Glycoprotein
• Optic Neuritis (immunology, pathology)
• Peptide Fragments (immunology)
• Peptides (immunology)
• Spinal Cord (immunology, pathology)