Localization of rabbit kappa light chain allotypic determinants.

The amino acid sequences of the constant regions of rabbit kappa light chains (C kappa) are remarkably divergent. The K1 allotypes differ at 47 of 106 positions; the K1 and K2 isotypes differ at three additional positions. Variability and structural dissimilarity plots reveal that most of these differences occur in clusters. Major hydrophilic areas are also found near some of these clusters. The structures of rabbit C kappa are modeled using the known alpha-carbon backbone structure of the Fab fragment of mouse myeloma protein McPC603. The effect of sequence variations upon the hypothetical three-dimensional structures was assessed and immunogenic determinants predicted and located. It was found that predicted determinants were external and located in or near loops. Two clusters of potentially interacting regions were predicted. Within each there could be several "topographical" and overlapping sets of epitopes that are recognized by different antibody-combining sites. One of the predicted immunogenic sites clearly interacts with the CH1 domain of the heavy chain. A heavy-chain dependent serological determinant has been correlated with amino acid differences in this region (kappa chain positions 121 and 124).