THE MOAB-V-KAPPA-IIIB CROSS-REACTIVE IDIOTOPE ON A27A (HUMKV325) ENCODED KAPPA-CHAINS MAPS TO FRAMEWORK REGION-3

The monoclonal antibody MoAb-V kappa IIIb binds a cross-reactive idiot opic (CRI) determinant on light (L) chains encoded by the V kappa IIIb subgroup A27a (Humkv325) gene segment. The aim of this study was to l ocalize the MoAb-V kappa IIIb CRI. Mutational analyses involving regio n exchanges between a CRI-positive V kappa IIIb chain and a CRI-negati ve 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-po sitive kappa chains unpaired with a heavy (H) chain are reactive with MoAb-V kappa IIIb, indicating that the CRI is located on the kappa cha in alone without involvement of H chain residues. Combinatorial antibo dies composed of nonparental L and H chain pairings are reactive with MoAb-V kappa IIIb only when the L chain is A27a (Humkv325) encoded. Th e CRI, therefore, is not readily perturbed by H chain interactions. Wh en the FR3 from a CRI-positive kappa chain replaced the FR3 in a CRI-n egative lambda chain, the determinant was no longer detectable with Mo Ab-V kappa IIIb. It is possible, therefore, to exchange regions betwee n kappa chains from different families and retain the CRI structure, h owever the determinant is lost when placed in a more foreign backgroun d such as a lambda chain. These data more precisely define the interac tion between MoAb-V kappa IIIb and its CRI, and indicate that there ar e limits within which antibody FRs can be shuffled and still retain th eir native structural features.