Preferential T-cell receptor β-chain variable gene use in myelin basic protein-reactive T-cell clones from patients with multiple sclerosis

Abstract

Multiple sclerosis is an autoimmune disease in which T lymphocytes reactive to myelin basic protein (BP) could play a central role. T cells specific for BP were cloned from the blood of multiple sclerosis patients and normal individuals, and expression of T-cell receptor variable region genes was analyzed. A remarkable bias for use of β-chain variable region (Vβ) 5.2 and, to a lesser extent, Vβ6.1 was seen among BP-specific clones from patients but not from controls. The preferential use of Vβ5.2 for BP recognition did not reflect altered expression of this Vβ in the peripheral repertoire. Interestingly, shared Vβ5.2 usage was apparent for clones specific for different BP determinants, even when derived from the same individual. The concurrent demonstration by others (J. R. Oksenberg, M. A. Panzara, A. B. Begovich, H. Erlich, R. Murray, M. Sherritt, S. Stuart, C. C. Bernard, and L. Steinman, personal communication) that T cells within demyelinating areas of multiple sclerosis brains preferentially express Vβ5.2 and Vβ6.1 suggests that the BP-specific clones derived from blood may be relevant to disease pathogenesis. These findings may have important implications for the treatment of multiple sclerosis.