Immunogenicity of mitochondrial DNA modified by hydroxyl radical.
Mitochondria consume about 90 percent of oxygen used by the body, and are a particularly rich source of reactive oxygen species (ROS). In this research communication mitochondrial DNA (mtDNA) was isolated from fresh goat liver and modified in vitro by hydroxyl radical generated from UV irradiation (254 nm) of hydrogen peroxide. As a consequence of hydroxyl radical modification, mtDNA showed hyperchromicity and sensitivity to nuclease S1 digestion as compared to control mtDNA. Animals immunized with mtDNA and ROS-modified mtDNA induced antibodies as detected by direct binding and competition ELISA. The data suggest that immunogenicity of mtDNA got augmented after treatment with hydroxyl radical. IgG isolated from immune sera showed specificity for respective immunogen and cross-reaction with other nucleic acids. Binding of induced antibodies with array of antigens clearly indicates their polyspecific nature. Moreover, the polyspecificity exhibited by induced antibodies is unique in view of similar multiple antigen binding properties of naturally occurring anti-DNA antibodies derived from SLE patients.
Alam
Khurshid
K
Department of Biochemistry, Faculty of Medicine, J.N. Medical College, A.M.U., Aligarh 202 002, India. kalam786@rediffmail.com
Moinuddin
Jabeen
Suraya
S
D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D004249:DNA Damage / Q000276:immunology*; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000276:immunology* / Q000528:radiation effects*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006041:Goats; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000528:radiation effects; D017665:Hydroxyl Radical / Q000737:chemistry* / Q000276:immunology / Q000633:toxicity; D007106:Immune Sera / Q000737:chemistry / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000209:etiology / Q000276:immunology; D008930:Mitochondria, Liver / Q000737:chemistry / Q000378:metabolism; D009690:Nucleic Acid Conformation / Q000528:radiation effects; D009691:Nucleic Acid Denaturation / Q000528:radiation effects; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology
D001323:Autoantibodies; D004272:DNA, Mitochondrial; D007106:Immune Sera; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide