Autoimmunogenicity of the helix-loop-helix DNA-binding domain

Petrakova, N., Gudmundsdotter, L., Yermalovich, M., Belikov, S., Eriksson, L. E., Pyakurel, P., Johansson, O., Biberfeld, P., Andersson, S. & Isaguliants, M. (2009). Autoimmunogenicity of the helix-loop-helix DNA-binding domain. Molecular Immunology, 46(7), pp. 1467-1480. doi: 10.1016/j.molimm.2008.12.013

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Abstract

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 compoments. 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.

Item Type: Article
Uncontrolled Keywords: DNA-binding domain, reverse transcriptase, anti-DNA autoantibody, heterochromatin, histones, proteinuria, nephropathy, thrombocytopenia
Subjects: Q Science > QR Microbiology > QR180 Immunology
Divisions: School of Health Sciences > Department of Adult Nursing
URI: http://openaccess.city.ac.uk/id/eprint/3494

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