A murine nephritogenic monoclonal anti-DNA autoantibody binds directly to mouse laminin, the major non-collagenous protein component of the glomerular basement membrane.
The interaction of the murine monoclonal anti-DNA antibody H241 with extracellular glomerular antigens was found to be due to the binding of this antibody to laminin, the major non-collagenous protein constituent of the glomerular basement membrane. This interaction is specific, since it is inhibited by laminin, double-stranded DNA and single-stranded DNA in solution. Furthermore, the binding of H241 to mouse laminin is mediated by conformational properties of the antigen because mild denaturation of laminin strongly decreases the binding capacity of H241, while exposure of laminin to sodium dodecyl sulfate, completely abolishes this interaction. H241 is able to bind to both, human and mouse laminin. These findings are in agreement with the ligand binding specificities of the autoantibodies spontaneously produced, that differ from those generated by artificial immunization. We conclude that the polyreactivity of H241 that confers to it the capacity to bind laminin, may account for its ability to form immune deposits by binding directly to non-DNA glomerular antigens.
Ludwig Institute for Cancer Research, São Paulo, Brasil.
J
J
Sabbaga
S R
SR
Line
P
P
Potocnjak
M P
MP
Madaio
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis*; D000911:Antibodies, Monoclonal / Q000032:analysis*; D000918:Antibody Specificity; D001485:Basement Membrane / Q000276:immunology / Q000378:metabolism; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D004247:DNA / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism*; D007797:Laminin / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007797:Laminin; D004247:DNA