title: The MoAb-V kappa IIIb cross-reactive idiotope on A27a (Humkv325) encoded kappa chains maps to framework region 3. off.
abstract: The monoclonal antibody MoAb-V kappa IIIb binds a cross-reactive idiotopic (CRI) determinant on light (L) chains encoded by the V kappa IIIb subgroup A27a (Humkv325) gene segment. The aim of this study was to localize the MoAb-V kappa IIIb CRI. Mutational analyses involving region exchanges between a CRI-positive V kappa IIIb chain and a CRI-negative V kappa 1 chain indicate that the MoAb-V kappa IIIb CRI is located in framework region (FR) 3 of A27a (Humkv325) encoded L chains. CRI-positive kappa chains unpaired with a heavy (H) chain are reactive with MoAb-V kappa IIIb, indicating that the CRI is located on the kappa chain alone without involvement of H chain residues. Combinatorial antibodies composed of non-parental L and H chain pairings are reactive with MoAb-V kappa IIIb only when the L chain is A27a (Humkv325) encoded. The CRI, therefore, is not readily perturbed by H chain interactions. When the FR3 from a CRI-positive kappa chain replaced the FR3 in a CRI-negative lambda chain, the determinant was no longer detectable with MoAb-V kappa IIIb. It is possible, therefore, to exchange regions between kappa chains from different families and retain the CRI structure, however the determinant is lost when placed in a more foreign background such as a lambda chain. These data more precisely define the interaction between MoAb-V kappa IIIb and its CRI, and indicate that there are limits within which antibody FRs can be shuffled and still retain their native structural features.
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-9140, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: Potter
authors.forename: Y C
authors.initials: YC
authors.lastname: Li
authors.forename: G N
authors.initials: GN
authors.lastname: Abraham
authors.forename: J D
authors.initials: JD
authors.lastname: Capra
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D000917:Antibody Formation; D001483:Base Sequence; D003429:Cross Reactions; D004252:DNA Mutational Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000235:genetics* / Q000276:immunology*; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data
chemical_list: D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains