Oral Presentations - Pathology and Laboratory Medicine - University ...

Post-doctoral FellowAbstract # 75Annelein Stax, Lenka Allan, Dong Jun Zheng, Peter van den ElzenDepartment of Pathology, University of British Columbia, Vancouver, CanadaAnnelein Staxsulfatide-reactive t cells in multiple sclerosisBackround/ObjectivesMultiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. The majority ofmyelin consists of lipids (70 percent). These lipids are presented by antigen presenting cells (APC) via CD1 moleculesand recognized by CD1-restricted T cells. Apolipoprotein E (ApoE), a lipoprotein present in cerebrospinal fluid, hasbeen shown to promote capture and presentation of lipids.MethodsLipids were isolated from bovine brain myelin using sucrose density ultracentrifugation, chloroform:methanolextraction and purification using an aminopropyl and C18 column. Also, commercially available lipids or synthesizedsulfatide were used. Lipid presentation was studied by culturing CD1-restricted T cells with CD1-transfected K562cells in the presence or absence of ApoE.ResultsFrom all studied commercially available myelin lipids, only sulfatide showed to induce IFN-gamma productionby CD1-restricted T cells. This activity was reduced when adding anti-CD1 blocking antibodies to the culture.Treatment of sulfatide with HCl removed the sulfate group, resulting in galactocerebroside and reduced the reactivityof the lipid. Similar results were found when isolated myelin lipids from bovine brain or synthesized sulfatide wereused. The later one also demonstrated enhanced reactivity when cultured in the presence of ApoE.ConclusionSulfatide, one of the most abundant lipids in myelin, is presented to human CD1-restricted T cells and ApoE canenhance this presentation. This implies that sulfatide could be a potential autoantigen in MS. In addition, ApoE mayplay a role in mediating an immune response against myelin lipids. These findings have important implications for thepathogenesis of MS and the development of new therapeutic applications.86 2 0 1 0 * P o s t e r P r e s e n t a t i o n s