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Biotech / Medical : Neurocrine Biosciences (NBIX) -- Ignore unavailable to you. Want to Upgrade?

To: Miljenko Zuanic who wrote (156)	4/29/1999 3:25:00 PM
From: scaram(o)uche	Respond to of 1834

J Immunol 1999 Mar 15;162(6):3336-41 Suppressive immunization with DNA encoding a self-peptide prevents autoimmune disease: modulation of T cell costimulation. Ruiz PJ, Garren H, Ruiz IU, Hirschberg DL, Nguyen LV, Karpuj MV, Cooper MT, Mitchell DJ, Fathman CG, Steinman L Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, CA 94305, USA. 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.

To: Miljenko Zuanic who wrote (156)	4/29/1999 3:27:00 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 1834

J Exp Med 1999 Apr 19;189(8):1275-84 Microbial epitopes act as altered peptide ligands to prevent experimental autoimmune encephalomyelitis. Ruiz PJ, Garren H, Hirschberg DL, Langer-Gould AM, Levite M, Karpuj MV, Southwood S, Sette A, Conlon P, Steinman L Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA. [Medline record in process] Molecular mimicry refers to structural homologies between a self-protein and a microbial protein. A major epitope of myelin basic protein (MBP), p87-99 (VHFFKNIVTPRTP), induces experimental autoimmune encephalomyelitis (EAE). VHFFK contains the major residues for binding of this self-molecule to T cell receptor (TCR) and to the major histocompatibility complex. Peptides from papilloma virus strains containing the motif VHFFK induce EAE. A peptide from human papilloma virus type 40 (HPV 40) containing VHFFR, and one from HPV 32 containing VHFFH, prevented EAE. A sequence from Bacillus subtilis (RKVVTDFFKNIPQRI) also prevented EAE. T cell lines, producing IL-4 and specific for these microbial peptides, suppressed EAE. Thus, microbial peptides, differing from the core motif of the self-antigen, MBPp87-99, function as altered peptide ligands, and behave as TCR antagonists, in the modulation of autoimmune disease.