Antibodies of different specificities are self-binding: implication for antibody diversity.
Antibodies of the S107/T15 germline family possess variable region structures which allow them to form specific complexes. We extended the investigation of the immunochemical properties of self-binding antibodies (autobodies) to mutant antibodies: U4, which binds DNA, and U10, which has no identified antigenic specificity. U4 differs from the germline S107/TEPC15 autobody by one substitution in the variable heavy chain, which results in a loss of phosphorylcholine binding. Like TEPC15, U4 and U10 are also self-binding. While self-binding of the wild-type TEPC15 antibody is inhibited by free hapten phosphorylcholine self-binding of the anti-DNA antibody U4 is inhibited by DNA and by free nucleotides. The self-binding locus of U4 and U10 was further investigated using peptides derived from the variable region. A 22 residue peptide from the CDR2/FR3 variable heavy chain sequence of the TEPC15 germline structure specifically inhibits self-binding in solid-phase assays. Peptides from unrelated antibodies have no effect on self-binding. The finding of antibodies with identical specificities which are self-binding or not self-binding demonstrates the existence of a novel kind of antibody repertoire diversity controlled by variable sequence structures.
Kaveri
S V
SV
IDEC Pharmaceuticals Corporation, La Jolla, CA 92037.
Halpern
R
R
Kang
C Y
CY
Köhler
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000916:Antibody Diversity; D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D001667:Binding, Competitive; D004247:DNA / Q000276:immunology; D007124:Immunoenzyme Techniques; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011863:Radioimmunoassay; D014407:Tumor Cells, Cultured
D001323:Autoantibodies; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D004247:DNA