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Systemic lupus erythematosus in mice, spontaneous and induced, is associated with autoimmunity to the C-terminal domain of p53 that recognizes damaged DNA.
Herkel, J; Erez-Alon, N; Mimran, A; Wolkowicz, R; Harmelin, A; Ruiz, P; Rotter, V; Cohen, I R.
Afiliação
  • Herkel J; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Eur J Immunol ; 30(4): 977-84, 2000 Apr.
Article em En | MEDLINE | ID: mdl-10760784
The tumor suppressor molecule p53 features a regulatory domain at the C terminus that recognizes damaged DNA. Since damaged DNA might be involved in activating anti-DNA autoantibodies, we tested whether autoimmunity to the C terminus of p53 might mark murine systemic lupus erythematosus (SLE). We now report that MRL / MpJ-Fas(lpr) mice, which spontaneously develop SLE, produce antibodies both to the C terminus of p53 and to a monoclonal antibody (PAb-421) that binds the p53 C terminus. Anti-idiotypic antibodies to PAb-421 (sampled as monoclonal antibodies) could also bind DNA. Thus, the PAb-421 antibody mimics DNA, and the anti-idiotypic antibody to PAb-421 mimics the p53 DNA-binding site. This mimicry was functional; immunization of BALB / c mice to PAb-421 induced anti-DNA antibodies and antibodies to the C terminus of p53, and most of the mice developed an SLE-like disease. Immunization of C57BL / 6 mice to PAb-421 induced antibodies to p53, but not to its C-terminal domain. The C57BL / 6 mice also did not develop anti-DNA antibodies or the SLE-like disease. Thus, network autoimmunity to the domain of p53 that recognizes damaged DNA can be a pathogenic feature in SLE in genetically susceptible strains of mice.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoanticorpos / Dano ao DNA / Proteína Supressora de Tumor p53 / Lúpus Eritematoso Sistêmico Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2000 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autoanticorpos / Dano ao DNA / Proteína Supressora de Tumor p53 / Lúpus Eritematoso Sistêmico Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2000 Tipo de documento: Article