51. Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis.
- Author
-
Krishnamoorthy, Gurumoorthy, Saxena, Amit, Mars, Lennart T., Domingues, Helena S., Mentele, Reinhard, Ben-Nun, Avraham, Lassmann, Hans, Dornmair, Klaus, Kurschus, Florian C., Liblau, Roland S., and Wekerle, Hartmut
- Subjects
- *
T cells , *TRANSGENIC mice , *MULTIPLE sclerosis , *MAJOR histocompatibility complex , *AUTOIMMUNITY - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF