학술논문

Selection of an RNA molecule that mimics a major autoantigenic epitope of human insulin receptor.
Document Type
article
Source
Proceedings of the National Academy of Sciences of the United States of America. 92(6)
Subject
Biochemistry and Cell Biology
Biomedical and Clinical Sciences
Biological Sciences
Immunology
Immunization
Biotechnology
Vaccine Related
Autoimmune Disease
Diabetes
Development of treatments and therapeutic interventions
5.1 Pharmaceuticals
Animals
Antibodies
Monoclonal
Antibody Specificity
Antigen-Antibody Complex
Autoantigens
Base Sequence
Epitopes
Humans
Insulin Resistance
Mice
Molecular Sequence Data
Nucleic Acid Conformation
Oligoribonucleotides
Plasmids
RNA
Receptor
Insulin
Transcription
Genetic
ANTIBODY-RNA INTERACTION
AUTOIMMUNITY
IN VITRO SELECTION
RNA STRUCTURE
Language
Abstract
Autoimmunity often involves the abnormal targeting of self-antigens by antibodies, leading to tissue destruction and other pathologies. This process could potentially be disrupted by small ligands that bind specifically to autoantibodies and inhibit their interaction with the target antigen. Here we report the identification of an RNA sequence that binds a mouse monoclonal antibody specific for an autoantigenic epitope of human insulin receptor. The RNA ligand binds specifically and with high affinity (apparent Kd congruent to 2 nM) to the anti-insulin receptor antibody and not to other mouse IgGs. The RNA can also act as a decoy, blocking the antibody from binding the insulin receptor. Thus, it probably binds near the combining site on the antibody. Strikingly, the RNA cross-reacts with autoantibodies from patients with extreme insulin resistance. One simple explanation is that the selected RNA may structurally mimic the antigenic epitope on the insulin receptor protein. These results suggest that decoy RNAs may be used in the treatment of autoimmune diseases.