title: Prior exposure to superantigen can inhibit or exacerbate autoimmune encephalomyelitis: T-cell repertoire engaged by the autoantigen determines clinical outcome.
abstract: Experimental allergic encephalomyelitis (EAE) is inducible in experimental animals immunized with myelin basic protein (MBP), proteolipid protein (PLP) or their peptides. We compared T-cell responses to encephalitogenic epitopes of PLP(43-64) and MBP(Ac1-11) in a single mouse strain, (PL/J x SJL)F1. MBP(1-11)-specific T-cell hybridomas expressed predominantly TCR V beta 8 or V beta 4, while PLP(43-64)-specific hybridomas expressed a diverse TCR repertoire. To analyze the biologic significance of the TCR repertoire (limited vs. diverse) to disease susceptibility, we pretreated mice with a superantigen (SEB), and then induced disease with these autoantigens. Mice injected with SEB and immunized with MBP(Ac1-11) showed significant inhibition of EAE, whereas SEB-pretreated mice immunized with PLP(43-64) had an increased severity of EAE and developed a chronic disease. These data demonstrate that prior exposure to microbial superantigens can significantly alter the autoimmune disease course depending upon the TCR repertoire used by the autoantigen.
authors.affiliation: Department of Neurology, Harvard Medical School, Boston, MA, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Das
authors.forename: A
authors.initials: A
authors.lastname: Cohen
authors.forename: S S
authors.initials: SS
authors.lastname: Zamvil
authors.forename: H
authors.initials: H
authors.lastname: Offner
authors.forename: V K
authors.initials: VK
authors.lastname: Kuchroo
mesh_terms: D000818:Animals; D000917:Antibody Formation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D004676:Myelin Basic Protein / Q000276:immunology*; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D004768:Enterotoxins; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D010455:Peptides; D018089:Superantigens; C031818:enterotoxin B, staphylococcal