A RESTRICTED T-CELL RESPONSE TO MYELIN BASIC-PROTEIN (MBP) IS STABLE IN MULTIPLE-SCLEROSIS (MS) PATIENTS

The close resemblance of MS to the animal model experimental autoimmun e encephalomyelitis (EAE) has provided compelling data sustaining a pa thogenic role of circulating T cells reactive against MBP. T cell anti gen receptor (TCR) usage in EAE is commonly considered restricted; nev ertheless, dynamic changes of TCR usage correlate with the course of E AE, resulting in a limited repertoire during early stages of disease a ctivity followed by the recruitment of other T cells reactive against new determinants. Although a broader TCR repertoire mediates the respo nse to MBP in humans, a restricted intraindividual heterogeneity may o ccur in some MS patients. In the present study we characterize the res ponse to MBP in MS subjects with relapsing remitting disease from two sampling time points 12 months apart. MBP-specific T cell lines (TCL) were first generated from eight MS individuals and two healthy subject s. New TCL were obtained after 12 months from one control and three MS patients whose response, at the first time point, was directed agains t a single epitope. Interestingly, these three subjects had a stable a nd mild disease. Few TCL obtained at two time points from the MS indiv iduals recognized the same immunodominant epitope and shared identical TCR V beta sequences. In the control we could not detect a restrictio n of the repertoire. These findings suggest that in some MS patients w ith benign disease a predominant T cell response to a single determina nt may be detectable at different moments and is mediated by clonally expanded populations.