T cells with specificity for idiotypic determinants on human monoclonal autoantibodies in myasthenia gravis

The activation of T cells from 46 patients with myasthenia gravis and 28 healthy individuals by two human monoclonal autoantibodies was studied. B-cell clones were produced by transformation of peripheral lymphocytes from a patient using Epstein-Barr virus and subsequent cloning. Two myasthenia-specific autoantibodies, one anti-receptor-antibody and one antiidiotypic antibody, both carrying separate recurrent idiotopes, were used in this study. Single activated T cells were identified by their secretion of IL2 and IFN gamma using a cell enzyme-linked-immunosorbent technique. The idiotypic antibody activated T cells in patients but not in most of the controls at concentrations of 1 pg/ml and 10 pg/ml. High concentrations of antibody resulted in T-cell activation in both groups. A similar dose-response pattern was recorded using the antiidiotypic antibody. Incubation with the idiotypic antibody resulted in T-cell stimulation, measured as numbers of IFN gamma-secreting cells that exceeded the mean +2 SD of controls, in 78% of patients and in 7% of the healthy individuals (p less than 0.001). The antiidiotypic antibody activated T cells in 50% of patients and in 4% of the healthy individuals (p less than 0.001). T-cell activation measured as numbers of IL2-secreting cells showed a difference between patients and controls which was as significant as for IFN gamma secretion. The results demonstrate the presence of T cells with specificity for disease-specific determinants on idiotypic and antiidiotypic antibodies in myasthenia gravis.