RESUMEN

OBJECTIVE: This study was designed to clarify the internalization of anti-DNA antibodies (anti-DNA) into living cells in the pathogenesis of systemic lupus erythematosus (SLE) using anti-DNA monoclonal antibodies (mAbs). METHODS: Anti-DNA mAbs 9D7, 9D7D2, 9A4, 5E3F5, 12B3H2 and 6E11E3 were prepared by a standard hybridoma procedure to determine the interaction of anti-DNA with proteins in different types of cells. RESULTS: The anti-DNA mAbs reacted with two protein antigens (35 and 50 kDa) in the cells. The 35-kDa antigen was shown to have 100% homology with hnRNP A2. The arginine-glycine-rich domain in hnRNP A2 was found to be the reaction site, and the methylation of hnRNP A2 by PRMT1 (protein arginine methyltransferase 1) was increased by anti-DNA. Moreover, anti-DNA was demonstrated to bind and internalize into the cytoplasm and nucleus. CONCLUSION: Nuclear localizing anti-DNA may cross-react with hnRNP A2 to modulate the inflammatory responses and polarize immune reactions associated with SLE.

Asunto(s)

Anticuerpos Antinucleares/inmunología , Reacciones Antígeno-Anticuerpo , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/inmunología , Lupus Eritematoso Sistémico/inmunología , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/inmunología , Secuencia de Bases , Sitios de Unión , Línea Celular , Núcleo Celular/inmunología , Citoplasma/inmunología , Epítopos , Citometría de Flujo , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/metabolismo , Humanos , Células Jurkat , Metilación , Ratones , Microscopía Fluorescente , Datos de Secuencia Molecular , Proteína-Arginina N-Metiltransferasas/metabolismo , Ratas , Células Tumorales Cultivadas