Autoimmunogenicity of the helix-loop-helix DNA-binding domain.
Nonimmunogenic character of native DNA, and its high immunogenicity when presented in complex with the DNA-binding proteins indicate that the latter might contain molecular triggers of anti-DNA response. To find if this is the case, we have evaluated the autoimmunogenic potential of the main DNA-binding domain of HIV-1 reverse transcriptase that belongs to the canonical helix-loop-helix type. BALB/c mice were immunized with a peptide representing the domain, alone or in complex with the fragmented human DNA in the presence of an adjuvant. Mice were assessed for specific antibodies, autoantibodies against a panel of self-antigens; glomerular immunoglobulin deposition; and for the signs of autoimmune disease, such as proteinuria, and changes in the blood components. Immunization with the adjuvanted peptide-DNA complex induced autoantibodies against double-stranded DNA, histones, heterochromatin, and kidney proteins; glomerular IgG and IgA deposition; proteinuria; thrombocytopenia, and anemia. Altogether, this identifies the helix-loop-helix DNA-binding domain as one of the molecular triggers of autoimmunity to DNA and DNA-associated proteins. The experiments cast new light on the role of the DNA-binding retroviral proteins in the induction of autoimmunity, and on the origins of autoimmune complications in the microbial infections in general. It also implies that choosing the DNA-binding proteins as vaccine candidates should be done with precaution.
Petrakova
Natalia
N
Ivanovsky Institute of Virology, 123098 Moscow, Russia.
Gudmundsdotter
Lindvi
L
Yermalovich
Maryna
M
Belikov
Sergey
S
Eriksson
Lars
L
Pyakurel
Pawan
P
Johansson
Olle
O
Biberfeld
Peter
P
Andersson
Sören
S
Isaguliants
Maria
M
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology / Q000652:urine; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D015551:Autoimmunity / Q000276:immunology*; D001772:Blood Cell Count; D002467:Cell Nucleus / Q000276:immunology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000276:immunology*; D005260:Female; D018257:Helix-Loop-Helix Motifs / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007668:Kidney / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012194:RNA-Directed DNA Polymerase / Q000276:immunology; D051381:Rats
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D004268:DNA-Binding Proteins; D012194:RNA-Directed DNA Polymerase