title: Epitope recognition in histone H1 by SLE autoantibodies in the presence of a DNA-ligand.
abstract: To investigate the specificity of anti H1 antibodies peptides from the N- and C-domain of H1 and the synthetic oligonucleotide (AT)6 were complexed. Circular dichroism (CD) spectroscopy indicated that the free peptides H1(1-16), H1(204-218) and C(121-210) in low salt buffer assume a random structure but become helical when bound to the oligonucleotide. The structured and unstructured H1 fragments were then analyzed by enzyme linked immunosorbent assay (ELISA) with anti-H1 antibodies in sera from patients with systemic lupus erythematosis (SLE) and with the monoclonal anti-H1 antibody MRA-12 derived from MLR lpr/lpr autoimmune mice. Binding of these antibodies to H1(204-218) and C was inhibited to a level of 50% when these H1 peptides were complexed with (AT)6. When the same antibody was tested with H1 fragment GC(34-210), attachment to oligonucleotide (AT)6 did not influence antibody binding. Competition studies with liquid phase GC and C antigen against solid phase GC and C indicated that liquid phase GC was more efficient in displacing antibody binding reactivity than liquid phase C. The displacement effect of both liquid phase antigens was greatest against solid phase C. We conclude that anti-H1 autoantibodies are directed against an epitope located near the junction of the G- and C-domain which is exposed and not masked when H1 is bound to DNA.
authors.affiliation: Department of Radiotherapy, University of Stellenbosch, Faculty of Medicine, Tygerberg, Republic of South Africa.
authors.forename: P
authors.initials: P
authors.lastname: Creemers
authors.forename: M
authors.initials: M
authors.lastname: Monestier
authors.forename: L
authors.initials: L
authors.lastname: Böhm
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D002942:Circular Dichroism; D000939:Epitopes / Q000032:analysis*; D006657:Histones / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D009841:Oligonucleotides / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D006657:Histones; D008024:Ligands; D009841:Oligonucleotides