This study analyzed the stability of the myelin basic protein (MBP)-specific T-cell receptor (TCR) repertoire during the course of multiple sclerosis (MS) in three patients who were monitored for three years by gadolinium-enhanced magnetic resonance imaging. Bulk-culture T-cell lines (TCLs) were generated from 3-4 time points for each patient, including times of active and quiescent disease. TCR analysis of these TCLs indicated that both the V alpha and V beta usage was similar over time for each patient. Sequencing of TCRs demonstrated conserved complementarity-determining region 3 (CDR3) sequences within TCLs that expressed the same V alpha segment over time, although the J alpha usage was different for each TCR. This indicates that the population of MBP-reactive T-cells is changing during the course of MS, but that host and/or environmental factors may be selecting T-cells with particular MHC/peptide binding domains.