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  • Title: The MoAb-V kappa IIIb cross-reactive idiotope on A27a (Humkv325) encoded kappa chains maps to framework region 3. off.
    Author: Potter KN, Li YC, Abraham GN, Capra JD.
    Journal: Scand J Immunol; 1996 Oct; 44(4):305-13. PubMed ID: 8845022.
    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.
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