title: Amelioration of relapsing experimental autoimmune encephalomyelitis with altered myelin basic protein peptides involves different cellular mechanisms.
abstract: T-cells specific for a region of human myelin basic protein, amino acids 87-99 (hMBP87-99), have been implicated in the development of multiple sclerosis (MS) a demyelinating disease of the central nervous system. Administration of soluble altered peptide ligand (APL), made by substituting native residues with alanine at either positions 91(91K > A or A91) or 97 (97R > A or A97) in the hMBP87-99 peptide, blocked the development of chronic relapsing experimental autoimmune encephalomyelitis (R-EAE), in the SJL mouse. The non-encephalitogenic APL A91, appears to induce cytokine shifts from Th1 to Th2 in the target T-cells, whereas the encephalitogenic superagonist APL A97 causes deletion of the MBP87-99 responsive cells. Thus, single amino acid changes at different positions in the same peptide epitope can lead to APL capable of controlling auto-immune disease by different mechanisms.
authors.affiliation: Neurocrine Biosciences, San Diego, CA 92121, USA. amitabh-gaur@neurocrine.com
authors.forename: A
authors.initials: A
authors.lastname: Gaur
authors.forename: S A
authors.initials: SA
authors.lastname: Boehme
authors.forename: D
authors.initials: D
authors.lastname: Chalmers
authors.forename: P D
authors.initials: PD
authors.lastname: Crowe
authors.forename: A
authors.initials: A
authors.lastname: Pahuja
authors.forename: N
authors.initials: N
authors.lastname: Ling
authors.forename: S
authors.initials: S
authors.lastname: Brocke
authors.forename: L
authors.initials: L
authors.lastname: Steinman
authors.forename: P J
authors.initials: PJ
authors.lastname: Conlon
mesh_terms: D000818:Animals; D016923:Cell Death; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology / Q000494:pharmacology*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D012008:Recurrence; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D016207:Cytokines; D008024:Ligands; D004676:Myelin Basic Protein; D010446:Peptide Fragments