Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight skin mouse interact with similar epitopes.
We have generated for the first time monoclonal antibodies (mAbs) specific for topoisomerase I (topo I) from scleroderma patients, and tight skin mice which develop a scleroderma-like syndrome. The epitope specificity of these antibodies has been determined using a series of fusion proteins containing contiguous portions of topo I polypeptide. Western blot analysis demonstrated that both human and mouse mAbs bound strongly to fusion protein C encompassing the NH2-terminal portion of the enzyme, and weakly to fusion proteins F and G containing regions close to the COOH-terminal end of the molecule. This crossreactivity is related to a tripeptide sequence homology in F, G, and C fusion proteins. It is interesting that a pentapeptide sequence homologous to that in fusion protein C was identified in the UL70 protein of cytomegalovirus, suggesting that activation of autoreactive B cell clones by molecular mimicry is possible. Both human and mouse mAbs exhibiting the same antigen specificity, also share an interspecies cross-reactive idiotope. These data suggest that B cell clones producing antitopo autoantibodies present in human and mouse repertoire are conserved during phylogeny, and are activated during the development of scleroderma disease.
Muryoi
T
T
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
Kasturi
K N
KN
Kafina
M J
MJ
Cram
D S
DS
Harrison
L C
LC
Sasaki
T
T
Bona
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D015153:Blotting, Western; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D011993:Recombinant Fusion Proteins; D004264:DNA Topoisomerases, Type I