Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis

G Krishnamoorthy, A Saxena, LT Mars… - Nature medicine, 2009 - nature.com
G Krishnamoorthy, A Saxena, LT Mars, HS Domingues, R Mentele, A Ben-Nun, H Lassmann
Nature medicine, 2009nature.com
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 …
Abstract
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.
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