Epitopes described in "A GMCSF-neuroantigen fusion protein is a potent tolerogen in experimental autoimmune encephalomyelitis (EAE) that is associated with efficient targeting of neuroantigen to APC."

Article Authors:J Lori Blanchfield; Mark D Mannie
Article Title:A GMCSF-neuroantigen fusion protein is a potent tolerogen in experimental autoimmune encephalomyelitis (EAE) that is associated with efficient targeting of neuroantigen to APC.
Reference Detail
Reference ID:1019074
Abstract:Cytokine-NAg fusion proteins represent an emerging platform for specific targeting of self-antigen to particular APC subsets as a means to achieve antigen-specific immunological tolerance. This study focused on cytokine-NAg fusion proteins that targeted NAg to myeloid APC. Fusion proteins contained GM-CSF or the soluble extracellular domain of M-CSF as the N-terminal domain and the encephalitogenic 69-87 peptide of MBP as the C-terminal domain. GMCSF-NAg and MCSF-NAg fusion proteins were approximately 1000-fold and 32-fold more potent than NAg in stimulating antigenic proliferation of MBP-specific T cells, respectively. The potentiated antigenic responses required cytokine-NAg covalent linkage and receptor-mediated uptake. That is, the respective cytokines did not potentiate antigenic responses when cytokine and NAg were added as separate molecules, and the potentiated responses were inhibited specifically by the respective free cytokine. Cytokine-dependent targeting of NAg was specific for particular subsets of APC. GMCSF-NAg and MCSF-NAg targeted NAg to DC and macrophages; conversely, IL4-NAg and IL2-NAg fusion proteins, respectively, induced an 1000-fold enhancement in NAg reactivity in the presence of B cell and T cell APC. GMCSF-NAg significantly attenuated severity of EAE when treatment was completed before encephalitogenic challenge or alternatively, when treatment was initiated after onset of EAE. MCSF-NAg also had significant tolerogenic activity, but GMCSF-NAg was substantially more efficacious as a tolerogen. Covalent GMCSF-NAg linkage was required for prevention and treatment of EAE. In conclusion, GMCSF-NAg was highly effective for targeting NAg to myeloid APC and was a potent, antigen-specific tolerogen in EAE.
Affiliations:The Department of Microbiology and Immunology, East Carolina University, Brody School of Medicine, Greenville, North Carolina, USA.
Reference Type:Literature
PubMed ID:20007248
Journal:J Leukoc Biol
Journal Volume:87
Article Pages:509-21
Journal ISSN:0741-5400
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@e95031f;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@58ffefb3;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@ad1fe6b;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@60962859;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@22331c99;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@499a9259;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@42fe36cf
Article MeSH List:Animals; Antigen-Presenting Cells(cytology; immunology); Antigens(chemistry; immunology); Cell Differentiation; Disease Progression; Encephalomyelitis, Autoimmune, Experimental(immunology; prevention & control; therapy); Granulocyte-Macrophage Colony-Stimulating Factor(chemistry; immunology); Guinea Pigs; Macrophage Colony-Stimulating Factor(chemistry); Mice; Myelin Basic Protein(chemistry; immunology); Organ Specificity(immunology); Organic Chemicals(immunology); Protein Structure, Tertiary; Rats; Recombinant Fusion Proteins(immunology)
Curation Last Updated:2015-01-17 22:46:15