Modulation of murine systemic lupus erythematosus with peptides based on complementarity determining regions of a pathogenic anti-DNA monoclonal antibody.
Experimental systemic lupus erythematosus (SLE) can be induced in naive mice by immunization with a murine monoclonal anti-DNA antibody (mAb), 5G12, that bears a major idiotype designated 16/6 Id. Strain-dependent differences were observed in the proliferative responses of lymph node cells of mice immunized with two peptides based on the sequences of the complementarity determining region (CDR) 1 and 3 of mAb 5G12. The capacity of the peptides to bind to major histocompatibility complex class II molecules correlated with the proliferative responses. Immunization of high responder strains with the CDR-based peptides led to production of autoantibodies and clinical manifestations characteristic to experimental SLE. The CDR-based peptides could prevent autoantibody production in neonatal mice that were immunized later either with the peptide or with the pathogenic autoantibody. Furthermore, the peptides inhibited specific proliferation of lymph node cells of mice immunized with the same peptide, with mAb 5G12 or with the human mAb anti-DNA, 16/6 Id. Thus, the CDR-based peptides are potential candidates for therapy of SLE.
Waisman
A
A
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Ruiz
P J
PJ
Israeli
E
E
Eilat
E
E
Könen-Waisman
S
S
Zinger
H
H
Dayan
M
M
Mozes
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D004247:DNA / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007130:Immunoglobulin Idiotypes; D007668:Kidney / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes; D010446:Peptide Fragments; C516151:edratide; D004247:DNA