Epitopes described in "Suppressive immunization with DNA encoding a self-peptide prevents autoimmune disease: modulation of T cell costimulation."

Article Authors:P J Ruiz; H Garren; I U Ruiz; D L Hirschberg; L V Nguyen; M V Karpuj; M T Cooper; D J Mitchell; C G Fathman; L Steinman
Article Title:Suppressive immunization with DNA encoding a self-peptide prevents autoimmune disease: modulation of T cell costimulation.
Reference Detail
Reference ID:1014786
Abstract:Usually we rely on vaccination to promote an immune response to a pathogenic microbe. In this study, we demonstrate a suppressive from of vaccination, with DNA encoding a minigene for residues 139-151 of myelin proteolipid protein (PLP139-151), a pathogenic self-Ag. This suppressive vaccination attenuates a prototypic autoimmune disease, experimental autoimmune encephalomyelitis, which presents clinically with paralysis. Proliferative responses and production of the Th1 cytokines, IL-2 and IFN-gamma, were reduced in T cells responsive to PLP139-151. In the brains of mice that were successfully vaccinated, mRNA for IL-2, IL-15, and IFN-gamma were reduced. A mechanism underlying the reduction in severity and incidence of paralytic autoimmune disease and the reduction in Th1 cytokines involves altered costimulation of T cells; loading of APCs with DNA encoding PLP139-151 reduced the capacity of a T cell line reactive to PLP139-151 to proliferate even in the presence of exogenous CD28 costimulation. DNA immunization with the myelin minigene for PLP-altered expression of B7.1 (CD80), and B7.2 (CD86) on APCs in the spleen. Suppressive immunization against self-Ags encoded by DNA may be exploited to treat autoimmune diseases.
Affiliations:Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, CA 94305, USA.
Reference Type:Literature
PubMed ID:10092787
Journal:J Immunol
Journal Volume:162
Article Pages:3336-41
Journal ISSN:0022-1767
Article Chemical List:Autoantigens;Immunosuppressive Agents;Myelin Proteolipid Protein;Peptide Fragments;Vaccines, DNA;myelin proteolipid protein (139-151)
Article MeSH List:Animals; Autoantigens(administration & dosage; genetics; immunology); Base Sequence; Encephalomyelitis, Autoimmune, Experimental(etiology; immunology; prevention & control); Female; Immunosuppressive Agents(administration & dosage; immunology); Injections, Intramuscular; Lymphocyte Activation(genetics); Mice; Mice, Inbred Strains; Molecular Sequence Data; Myelin Proteolipid Protein(administration & dosage; genetics; immunology); Peptide Fragments(administration & dosage; genetics; immunology); T-Lymphocytes(immunology); Th1 Cells(immunology); Vaccines, DNA(administration & dosage; immunology)
Curation Last Updated:2015-07-30 20:30:29