Structural Considerations are Important when Performing Computer - Based Searches for Molecular Mimics

Myelin basic protein (MBP)-reactive T cells are thought to play an important role the autoimmune disease Multiple Sclerosis (MS). MBP is an abundant protein on the myelin sheath which has a role in both myelin sheath formation and stabilization. MS patients have autoantibodies and autoreactive T cells which recognize MBP as foreign and thus attack the myelin sheath, essentially short circuiting the nervous system. One important question is: how do MS patients obtain these autoreactive T cells? In the process of negative selection, T cells which recognize self-antigens are supposed to be deleted. A leading explanation is that molecular mimicry plays a role in the induction of autoimmunity. In this hypothesis, infections with viruses or bacteria which contain similar sequences as MBP stimulate a series of T cells which cross-react with self-MBP. Either these bacterial or viral infections remain in the host, allowing for the continual activation of autoreactive T cells. Or, the chronic destruction of the myelin sheath leads to increased MBP fragmentation and exposure of antigenic epitopes which cause the chronic stimulation of autoreactive T cells. In either case, it is thought that bacteria and/or viruses induce the autoimmune state and thus their identity is desired.