title: Drastic change in idiotypic but not antigen-binding specificity of an antibody by a single amino-acid substitution.
abstract: In proliferating B lymphocytes, somatic mutation of rearranged antibody variable (V)-region genes occurs at high frequency and may have a key role in the selection of these cells. It is of interest in this context to learn in which way single mutations can affect antigen binding and/or idiotypic specificity of an antibody. Previous investigations have analysed spontaneous mutants of myeloma and hybridoma cells in which the mutation affected the antigen-binding specificity of the antibody. Here we describe an antibody mutant that has fully retained antigen-binding specificity but has lost or drastically changed all V-region antigenic determinants (idiotopes) of the wild type as defined by monoclonal anti-idiotope antibodies. The mutant phenotype is generated by a glycine to arginine exchange in the middle of the diversity (D) element, at position 103 of the heavy chain.
authors.forename: A
authors.initials: A
authors.lastname: Radbruch
authors.forename: S
authors.initials: S
authors.lastname: Zaiss
authors.forename: C
authors.initials: C
authors.lastname: Kappen
authors.forename: M
authors.initials: M
authors.lastname: Brüggemann
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: K
authors.initials: K
authors.lastname: Rajewsky
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D000939:Epitopes; D006241:Haptens; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D007138:Immunoglobulin delta-Chains / Q000235:genetics / Q000276:immunology; D051379:Mice; D009154:Mutation; D009592:Nitrohydroxyiodophenylacetate / Q000276:immunology; D013329:Structure-Activity Relationship
chemical_list: D000939:Epitopes; D006241:Haptens; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D007138:Immunoglobulin delta-Chains; D009592:Nitrohydroxyiodophenylacetate