Human T cell responses to autoantibody variable region peptides

The origins and regulation of autoantibodies in SLE may involve idiotypic cell interactions. The purpose of this study was to determine if SLE patients have T cells reactive with the idiotopes of autoantibodies. Sequences of the variable regions of two DNA-binding autoantibodies (V lambda of antibody B3 and VH of 9G4) were selected according to the predicted location of their idiotypes defined previously by anti-idiotypic antibodies. The sequences were prepared as synthetic 16mer peptides (idiopeptides). Peripheral blood mononuclear cells were prepared from SLE patients (n = 28) and controls (n = 13) and put into multiple microcultures with idiopeptide for 6 days. The frequency of responding cultures was determined as those incorporating thymidine at levels above the mean plus three standard deviations of the control cultures lacking peptide. Of the 28 lupus patients, six responded to B3 idiopeptide and five to the 9G4 idiopeptide. Some patients responded to other idiopeptides, but only one normal individual responded to each reference peptide. The difference between the patient and control responses to all idiopeptides was significant by chi 2 analysis (P = 0.025). We conclude that patients with SLE show evidence of sensitisation of T cells to idiotopes of autoantibodies. Such anti-idiotypic T cells could either provide idiotype-specific help or suppression for autoantibody responses in SLE.