Molecular Identification of Pathogenetic Id^LNF⁺₁ Autoantibody Idiotypes Derived from the (NZB×SWR)F₁ Model for Systemic Lupus Erythematosus

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• 作者：Price ; Karen ; Knupp ; Corey J. ; Tatum ; Arthur H. ; Jiang ; Feng ; Stoll ; Matthew ; Gavalchin ; Jerrie
• 刊名：Journal of Autoimmunity
• 出版年：2002
• 出版时间：November, 2002
• 年：2002
• 卷：19
• 期：3
• 页码：87-101
• 全文大小：931 K

文摘

The acceleration of nephritis in SNF₁ mice by CD4⁺ T-cell clones reactive with a nephritogenic idiotype, Id^LNF₁ [1], as well as the ability of anti-Id^LNF₁ antisera to down-regulate the production of Id^LNF⁺₁ immunoglobulin (Ig) in vivo and delay nephritis [2], suggests that dysregulation of this idiotype may contribute to the development of SNF₁ nephritis. Herein, we show that a monoclonal Id^LNF₁-expressing antibody, 540, significantly (P≤ 0.01) stimulated Id^LNF₁-reactive T-cell clones B6 and D2 to proliferate, while other Id^LNF+1 antibodies did not. Further, injection of 540-producing hybridoma cells into nonautoimmune (SWR×Balb/c)F₁ mice resulted in the deposition of Id^LNF⁺₁ Ig in the kidneys, in a pattern indicative of early nephritis. To identify the pathogenetic Id^LNF₁ 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 Id^LNF₁-expressing Igs 540, 317, and 533. Two overlapping peptides derived from the V_H 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 Id^LNF₁-expressing Ig in SNF₁ nephritis.