title: Molecular identification of pathogenetic IdLNF+1 autoantibody idiotypes derived from the NZBxSWR F1 model for systemic lupus erythematosus.
abstract: The acceleration of nephritis in SNF(1) mice by CD4(+) T-cell clones reactive with a nephritogenic idiotype, Id(LN)F(1) [1], as well as the ability of anti-Id(LN)F(1) antisera to down-regulate the production of Id(LN)F(+)(1) immunoglobulin (Ig) in vivo and delay nephritis [2], suggests that dysregulation of this idiotype may contribute to the development of SNF(1) nephritis. Herein, we show that a monoclonal Id(LN)F(1)-expressing antibody, 540, significantly (P< or = 0.01) stimulated Id(LN)F(1)-reactive T-cell clones B6 and D2 to proliferate, while other Id(LN)F+1 antibodies did not. Further, injection of 540-producing hybridoma cells into nonautoimmune (SWRxBalb/c)F(1) mice resulted in the deposition of Id(LN)F(+)(1) Ig in the kidneys, in a pattern indicative of early nephritis. To identify the pathogenetic Id(LN)F(1) 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(LN)F(1)-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 SNF(1) T cells and T-cell clones B6 and D2. These results further support the involvement of a subset of Id(LN)F(1)-expressing Ig in SNF(1) nephritis.
authors.affiliation: Program of Cell and Molecular Biology, SUNY Upstate Medical University, 750 E. Adams Street, Syracuse, NY 13210, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Price
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Knupp
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Tatum
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.forename: Matthew
authors.initials: M
authors.lastname: Stoll
authors.forename: Jerrie
authors.initials: J
authors.lastname: Gavalchin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D001483:Base Sequence; D004195:Disease Models, Animal; D005260:Female; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes