Endopeptidase modulated autoimmunity

Myelin basic (MBP) protein can induce experimental autoimmune encephalomyelitis (EAE) and has been implicated in the suggested autoimmune component in multiple sclerosis. But, the mechanism by which autoreactive T cells escape tolerance induction to MBP remains unknown. Two papers in January 14 online Nature Immunology show that dominant MBP epitopes prevents autoimmunity and can be hidden from T cells by the action of an asparagine endopeptidase.

Stephen Anderton and colleagues from University of Edinburgh, UK, demonstrated that MBP contains three overlapping but distinct epitopes. They showed that only activation of T cells specific for either of the minor MBP(89–94) or MBP(95–101) epitopes resulted in EAE, whereas immunization with the dominant MBP(92–98) epitope did not induce autoimmunity (Nat Immunol 2002, DOI: 10.1038/ni756).

In the second paper, Bénédicte Manoury and colleagues from University of Dundee, UK, observed that the destructive processing by asparagine endopeptidase (AEP) limits the presentation of the dominant MBP ...