CLONAL EXPANSION OF MYELIN BASIC PROTEIN-REACTIVE T-CELLS IN PATIENTSWITH MULTIPLE-SCLEROSIS - RESTRICTED T-CELL RECEPTOR-V GENE REARRANGEMENTS AND CDR3 SEQUENCE

Myelin basic protein (MBP)-reactive T cells are thought to play an imp ortant role in the pathogenesis of multiple sclerosis (MS). In some pa tients with MS, these autoreactive T cells display a limited heterogen eity in their epitope recognition and T cell receptor (TCR) variable ( V) gene usage. These individual-dependent properties of MBP-reactive T cells have led to the speculation that they may represent clonal expa nsion in vivo in some MS patients. In the present study, 51 MBP-reacti ve T cell clones derived from patients with MS and healthy individuals were examined for their epitope recognition and the TCR V alpha and V beta gene rearrangements. The V gene junctional region sequences of i dentified alpha and beta genes were further analyzed to probe their cl onal origins, as the sequences are unique for individual clones. Our d ata showed that 26 clones derived from nine patients with MS shared a predominant reactivity to the immunodominant regions of MBP, 84-102 11 0-129 and 143-168, and used various TCR V alpha and V beta rearrangeme nts. The V gene usage of the clones was restricted to certain V alpha V beta combination(s) in a given MS patient, but varied among differen t patients. The sequence analysis revealed that the clones generated f rom a given patient shared a limited or a single junctional region seq uence pattern(s), indicating their oligoclonal or monoclonal origin(s) . In contrast, 25 MBP-reactive T cell clones derived from normal indiv iduals exhibited unfocused epitope recognition and V gene usage. Thus, the limited heterogeneity of MBP-reactive T cells in their structural and functional characteristics reflects their clonal expansion in viv o in some patients with MS.