Analysis of antibody-antigen and antibody-anti-(idiotypic antibody) cross-reactivity using synthetic peptide probes.
The extent, nature and structural basis of immunological cross-reactivity of an anti-synthetic peptide monoclonal antibody (MAb) with the parent antigen (influenza virus haemagglutinin) from which the peptide was derived, and with a paratope-directed anti-idiotypic (anti-Id) antibody was investigated. Use of synthetic homologs and analogs of the peptide indicated that the anti-peptide MAb utilizes a common binding site to complex with peptide, haemagglutinin (HA) and anti-Id antibody, and the affinity constants for the binding of the anti-peptide MAb to peptide and to the anti-Id MAb were found to differ only by three fold. Determination of the amino acid sequence of the heavy chain variable domain (VH) of the anti-Id MAb did not reveal any obvious sequence homology with the peptide. Consideration of the spatial arrangement of residues, however, disclosed a region within the framework of the anti-Id VH with similarity to the epitope recognized by the anti-peptide MAb. This region, formed from antiparallel chains, contains amino acid residues arranged in a conformation similar to that assumed by amino acid residues comprising the epitope within the intact HA.
McInerney
T L
TL
Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
Brown
L E
LE
Sutton
V R
VR
Jackson
D C
DC
D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology*; D000937:Antigen-Antibody Reactions / Q000276:immunology; D001483:Base Sequence; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D013329:Structure-Activity Relationship
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments