HUMAN T-CELL RESPONSES TO AUTOANTIBODY VARIABLE REGION PEPTIDES

The origins and regulation of autoantibodies in SLE may involve idioty pic cell interactions. The purpose of this study was to determine if S LE 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-idio typic antibodies. The sequences were prepared as synthetic 16mer pepti des (idiopeptides). Peripheral blood mononuclear cells were prepared f rom 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 ab ove the mean plus three standard deviations of the control cultures la cking peptide. Of the 28 lupus patients, six responded to B3 idiopepti de and five to the 9G4 idiopeptide. Some patients responded to other i diopeptides, but only one normal individual responded to each referenc e peptide. The difference between the patient and control responses to all idiopeptides was significant by chi(2) analysis (P = 0.025). We c onclude that patients with SLE show evidence of sensitisation of T cel ls to idiotopes of autoantibodies. Such anti-idiotypic T cells could e ither provide idiotype-specific help or suppression for autoantibody r esponses in SLE.