Identification of autoimmune T cells among in vivo expanded CD25(+) T cells in multiple sclerosis

Although clonal expansion of autoimmune T cells has been reported in multip le sclerosis (MS), very limited information is available on specificities, clonal size, or activation state of the expanded clones. Here we address th e issue of clonal expansion by using a novel technique demonstrating clonot ypes defined by single-strand conformation polymorphism of TCR beta-chain c DNAs, Examination of activated T cells (CD3(+)CD25(+)) isolated from the pe ripheral blood of MS revealed limited numbers (20-82) of expanded clones de fined by single-strand conformation polymorphism clonotype. To estimate the Ag specificities of dominant clonotypes in the activated T cells, these sa mples were examined in parallel with Th1 T cell clones specific for myelin basic protein or proteolipid protein (PLP) derived from the same patients. Analysis of two patients demonstrated that the dominant clonotypes would co ntain those specific for myelin basic protein or PLP. Although the majority of the clonotypes could be detected only transiently, a PLP95-116-specific clonotype was found to persist for over 1 yr. Thus, single-strand conforma tion polymorphism clonotype analysis allows us to monitor the kinetics of g iven T cell clones in vivo and could provide useful information for designi ng clonotype (Id)-specific manipulation of human diseases such as MS.