Characterization of the encephalitogenic immune response in a model of multiple sclerosis.
Experimental autoimmune encephalomyelitis (EAE) can be actively induced with the extracellular domain of myelin oligodendrocyte glycoprotein (MOG 1-125). MOG-EAE closely mimics multiple sclerosis (MS) especially as far as demyelination, lesion formation and axonal pathology are concerned. MOG 91-108 is the encephalitogenic stretch within MOG 1-125 in two EAE-susceptible MHC congenic LEW rat strains [LEW.1AV1 (RT1(av1)) and LEW.1N (RT1(n))] and DA (RT1(av1)) rats. In LEW.1AV1 rats, disease could be induced with MOG 96-104 and to a lesser extent with MOG 98-106, whereas in LEW.1N rats, only MOG 98-106 was pathogenic. Both peptides bound well to their restricting MHC class II molecules, i.e., RT1.D(n) in the LEW.1N rat and RT1.B(a) in the LEW.1AV1 rat. TCR spectratyping of MOG 91-108 immunized LEW.1N, LEW.1AV1 and DA rats revealed that MHC class II determined the TCRBV preference of CNS infiltrating T cells. The data demonstrate that the most critical factor in inducing MS like pathology is presentation of autoantigenic peptides on MHC class II molecules resulting in demyelination and axonal pathology.
Experimental Neuroimmunology Laboratory, Hertie Institute for Clinical Brain Research, Department of General Neurology, University of Tübingen, Tübingen, Germany.
Katrien L
KL
de Graaf
Silvia
S
Barth
Martin M
MM
Herrmann
Maria K
MK
Storch
Karl-Heinz
KH
Wiesmüller
Robert
R
Weissert
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D018604:Epitope Mapping; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology
D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta