A murine monoclonal anti-idiotype to anti-ribosomal P antibodies: production, characterization, and use in systemic lupus erythematosus.
Overt anti-ribosomal P (anti-P) autoantibodies are restricted to a subset of systemic lupus erythematosus (SLE) patients, and are potentially pathogenic. Covert anti-P are detected in all other individuals. An idiotype (Id) network is nonoperational in those with overt anti-P, whereas it is functional in all others. The aim of this study was to produce a murine monoclonal (mAb) anti-Id to characterize the anti-P Id network in SLE. BALB/c mice were immunized with F(ab')(2) fragments of IgG anti-P from a patient with a broadly cross-reactive Id. One mAb was chosen (mAb41) that reacted preferentially to the immunogen. This IgG1 mAb bound comparably in ELISAs to affinity-purified anti-P from 11 SLE patients with overt anti-P. This binding was partially inhibited with ribosomal P antigen. In contrast, it did not bind to affinity-purified control autoantibodies, nor to normal human IgG. mAb41 inhibited anti-P binding to ribosomal P antigen in immunoassays and on Jurkat cells. No change was detected in patients' anti-P antibodies over time when mAb41 was used in Id-specific ELISAs. We conclude that mAb41 is an anti-Id that recognizes a public idiotope within the antigen-combining site of anti-P antibodies. Thus, it is analogous to its human counterparts, and potentially, would modulate the pathogenicity of anti-P autoantibodies in vivo.
Pan
Z J
ZJ
Arthritis and Immunology Program, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Anderson
C J
CJ
Stafford
H A
HA
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D015551:Autoimmunity; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins; D012269:Ribosomal Proteins / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; C064601:L12E protein, Trypanosoma cruzi; D015800:Protozoan Proteins; D012269:Ribosomal Proteins