Hypothesized role of galactocerebroside and NKT cells in the etiology of multiple sclerosis.

Harvard College, 1129 Harvard Yard Mail Center, Cambridge, United States. mblewett@fas.harvard.edu

Medical hypotheses 2008

According to the molecular mimicry theory, multiple sclerosis (MS) develops when the immune system mistakenly attacks a component of the myelin sheath that is structurally similar to a foreign epitope. The glycolipid galactocerebroside (GalC) is a major component of myelin. As lipids comprise between 70% and 85% of myelin, glycolipids should be investigated as candidate autoantigens in MS. GalC displays broad structural similarities to the Borrelia burgdorferi glycolipid antigen BbGL-2 and to the Sphingomonas antigen GalAGSL. In principle, therefore, these bacteria may induce an autoimmune attack on the myelin sheath. GalC is also structurally similar to natural killer T (NKT) cell ligand alpha-galactosylceramide (alpha-GalCer). Further studies must be performed to clarify the role of GalC in the activation of NKT cells and the development of MS.