The acceleration of nephritis in SNF1 mice by CD4+ T-cell clones reactive with a nephritogenic idiotype, IdLNF1 , as well as the ability of anti-IdLNF1 antisera to down-regulate the production of IdLNF1+ immunoglobulin (Ig) in vivo and delay nephritis , suggests that dysregulation of this idiotype may contribute to the development of SNF1 nephritis. Herein, we show that a monoclonal IdLNF1-expressing antibody, 540, significantly (P≤0.01) stimulated IdLNF1-reactive T-cell clones B6 and D2 to proliferate, while other IdLNF1+ antibodies did not. Further, injection of 540-producing hybridoma cells into nonautoimmune (SWRxBalb/c)F1 mice resulted in the deposition of IdLNF1+ Ig in the kidneys, in a pattern indicative of early nephritis. To identify the pathogenetic IdLNF1 epitope(s) at the molecular level, we compared the deduced amino acid sequences of the heavy and light chain variable regions of pathogenetic and non-pathogenetic IdLNF1-expressing Igs 540, 317, and 533. Two overlapping peptides derived from the VH sequence of 540 (aa 54-66 and 62-73), which both contain the triple basic amino acid motif K(X)K(X)K, stimulated SNF1 T cells and T-cell clones B6 and D2. These results further support the involvement of a subset of IdLNF1-expressing Ig in SNF1 nephritis. © 2002 Elsevier Science Ltd. All rights reserved.