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T-cell response to myelin basic protein and lipid-bound myelin basic protein in patients with multiple sclerosis and
Benedetta Mazzanti1, Marco Vergelli1, Paolo Riccio2
1Neuroimmuology Branch, Room 5B16, Building 10, NINDS, NIH, 10 Center DR MSC 1400, Bethesda, MD 20892-1400, USA; Department of Neurological and Psychiatric Sciences, University of Florence, Viale Morgagni 85, 50134 Firenze, Italy.
Abstract:
An autoimmune T-cell response to myelin proteins is thought to be involved in the pathogenesis of multiple sclerosis (MS) and myelin basic protein (MBP) is the most widely studied potential target antigen. We investigated the T-cell response to MBP in MS patients and controls using two different molecular forms of the protein: the classical hydrophilic MBP (lipid-free MBP, LF-MBP) and a lipid-bound, native-like preparation of MBP isolated in a molecular form retaining the binding to all myelin lipids (lipid-bound-MBP, LB-MBP). Short term T-cell lines (TCL) were generated using either LF- or LB-MBP and tested for their reactivity to the in vitro stimulating antigen. No differences were detected between MS patients and healthy donors in the percentage of T-cell cultures responsive to the LF-MBP. In contrast, the number of LB-MBP reactive cultures was higher in MS patients than in controls. This difference was almost entirely due to the presence of high numbers of LB-MBP-specific TCL in MS patients which did not cross-react with LF-MBP and were not present in healthy subjects. LB-MBP may represent a novel antigen worth to be investigated in MS.