Inhibition of self-binding antibodies (autobodies) by a VH-derived peptide.
The self-binding properties of a dominant idiotypic antibody (T15) and a minor idiotypic antibody (M603), both specific for phosphorylcholine, were examined as models of self-binding antibodies (autobodies). Observed differences in the self-binding affinity of T15 and M603 relate to variable sequence differences in their respective heavy and light chains. A molecular recognition theory based on the translation of coding and noncoding DNA strands was used to identify complementary amino acid sequences responsible for self-binding. The second hypervariable region of the heavy chain domain, extending into the third framework region, was predicted as the primary self-binding locus. Among peptides synthesized with different variable heavy and light chain regions, a 24-residue peptide spanning the second hypervariable and third framework regions of the heavy chain of T15 was nearly as effective as phosphorycholine in inhibiting the self-binding complexes.
Kang
C Y
CY
IDEC Pharmaceuticals Corporation, La Jolla, CA 92037.
Brunck
T K
TK
Kieber-Emmons
T
T
Blalock
J E
JE
Kohler
H
H
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000276:immunology*; D002794:Choline / Q000494:pharmacology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D010455:Peptides / Q000494:pharmacology; D010767:Phosphorylcholine / Q000494:pharmacology; D011485:Protein Binding; D013329:Structure-Activity Relationship
D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D010455:Peptides; D010767:Phosphorylcholine; D002794:Choline