Intramolecular epitope spreading induced by staphylococcal enterotoxin superantigen reactivation of experimental allergic encephalomyelitis.
The staphylococcal enterotoxin superantigens are among the most potent T cell stimulators known. They have been shown to alter the course of disease in experimental allergic encephalomyelitis, an animal model for multiple sclerosis (MS). We have previously demonstrated that two of the staphylococcal enterotoxins, SEA and SEB, are able to reactivate paralysis in PL/J mice which had been immunized with myelin basic protein (MBP) and resolved an initial episode of paralysis. In PL/J mice, Ac1-11 is the dominant encephalitogenic determinant of MBP. We hypothesized that superantigen reactivation of experimental allergic encephalomyelitis (EAE) may result in the spreading of T cell specificities for other epitopes of MBP. PL/J mice which had resolved an initial episode of EAE were treated with SEA and developed a second episode of paralysis. At the onset of symptoms, mice were sacrificed and splenocytes were stimulated in vitro with a panel of MBP peptides. EAE reactivation by SEA resulted in the spreading of T cell specificites to residues 100 to 120 of MBP. While intramolecular spreading did occur, spreading to other antigens did not, as evidenced by the lack of response to a proteolipid protein (PLP) peptide and heat shock protein 60 (hsp 60). To further characterize the epitope MBP 100-120, PL/J mice were immunized with MBP 100-120. No initial development of disease was observed. However, administration of SEA 2 weeks after MBP 100-120 immunization resulted in the onset of paralysis. In addition to a proliferative response to MBP 100-120, these mice also exhibited a proliferative response to the flanking MBP peptides 81-100 and 120-140. Thus, SEA is able to induce intramolecular epitope spreading in PL/J mice after reactivation of EAE.
Soos
Jeanne M
JM
Department of Microbiology and Cell Science, Box 110700, University of Florida, Gainesville, FL 32611, USA.
Mujtaba
Mustafa G
MG
Schiffenbauer
Joel
J
Torres
Barbara A
BA
Johnson
Howard M
HM
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology*; D000939:Epitopes; D007114:Immunization; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*
D004768:Enterotoxins; D000939:Epitopes; D004676:Myelin Basic Protein; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal