Prior exposure to superantigen can inhibit or exacerbate autoimmune encephalomyelitis: T-cell repertoire engaged by the autoantigen determines clinical outcome.
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.
Das
M R
MR
Department of Neurology, Harvard Medical School, Boston, MA, USA.
Cohen
A
A
Zamvil
S S
SS
Offner
H
H
Kuchroo
V K
VK
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*
D004768:Enterotoxins; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D010455:Peptides; D018089:Superantigens; C031818:enterotoxin B, staphylococcal