Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis.
We describe here the paradoxical development of spontaneous experimental autoimmune encephalomyelitis (EAE) in transgenic mice expressing a myelin oligodendrocyte glycoprotein (MOG)-specific T cell antigen receptor (TCR) in the absence of MOG. We report that in Mog-deficient mice (Mog-/-), the autoimmune response by transgenic T cells is redirected to a neuronal cytoskeletal self antigen, neurofilament-M (NF-M). Although components of radically different protein classes, the cross-reacting major histocompatibility complex I-Ab-restricted epitope sequences of MOG35-55 and NF-M18-30 share essential TCR contact positions. This pattern of cross-reaction is not specific to the transgenic TCR but is also commonly seen in MOG35-55-I-Ab-reactive T cells. We propose that in the C57BL/6 mouse, MOG and NF-M response components add up to overcome the general resistance of this strain to experimental induction of autoimmunity. Similar cumulative responses against more than one autoantigen may have a role in spontaneously developing human autoimmune diseases.
Krishnamoorthy
Gurumoorthy
G
Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany.
Saxena
Amit
A
Mars
Lennart T
LT
Domingues
Helena S
HS
Mentele
Reinhard
R
Ben-Nun
Avraham
A
Lassmann
Hans
H
Dornmair
Klaus
K
Kurschus
Florian C
FC
Liblau
Roland S
RS
Wekerle
Hartmut
H
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D003429:Cross Reactions; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000276:immunology*; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D016900:Neurofilament Proteins / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016900:Neurofilament Proteins; D011948:Receptors, Antigen, T-Cell; C061195:neurofilament protein M